Export file:

Format

  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text

Content

  • Citation Only
  • Citation and Abstract

CLEC receptors, endocytosis and calcium signaling

Susavion Biosciences, Inc., 1615 W. University Drive, Suite 132, Tempe, AZ 85281, USA

Proper immune system function is dependent on precisely evolved sensing and signal transduction events that occur at cellular and subcellular compartment boundaries. Recent immunotherapeutic efforts have generally focused on the roles that two specific protein superfamilies play in such events. This review is directed at a third superfamily, the C-type (Ca2+-dependent) lectin-type (CLEC) receptors and the nuanced, less traditionally acknowledged, yet quite important, role of endocytic-based calcium signaling. While extracellular recognition events rely heavily on the sophisticated structural diversity that lectins and glycobiology have to offer, the actual details of CLEC receptor-mediated, endocytic-based, calcium signal transduction have remained less appreciated. Because many CLEC receptor family members are emerging, not only as biomarkers for critical immune cell subpopulations, but also proving to be selective and pivotal modulators of immune function, this review seeks to promote the potential role CLEC receptor-initiated calcium signaling plays in immunotherapy. Given the importance of calcium signaling, these receptors provide a means to initiate a selective physiological response.
  Figure/Table
  Supplementary
  Article Metrics

References

1. Das S, Dawson NL, Orengo RA (2015) Diversity in protein domain superfamilies. Curr Opin Genet Dev 35: 40–49.     

2. Giuroiu I, Weber J (2017) Novel checkpoints and cosignaling molecules in cancer immunotherapy. Cancer J 23: 23–31.     

3. Wei SC, Levine JH, Cogdill AP, et al. (2017) Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade. Cell 170: 1120–1133.     

4. Murmann AE, McMahon KM, Haluck-Kangas A, et al. (2017) Induction of DISE in ovarian cancer cells in vivo. Oncotarget 8: 84643–84658.

5. Buchbinder E, Desai A (2016) CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol 39: 98–106.     

6. Rotte A, Jin JY, Lemaire V (2017) Mechanistic overview of immune checkpoints to support the rational design of their combinations in cancer immunotherapy. Ann Oncol. 

7. Zelensky AN, Gready JE (2005) The C-type lectin-like domain superfamily. FEBS J 272: 6179–6217.     

8. Geijtenbeek TB, Gringhuis SI (2009) Signaling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol 9: 465–479.     

9. García-Vallejo JJ, Van KY (2009) Endogenous ligands for C-type lectin receptors: the true regulators of immune homeostasis. Immunol Rev 230: 22–37.     

10. Van KY, Ilarregui JM, van Vliet SJ (2015) Novel insights into the immunomodulatory role of the dendritic cell and macrophage-expressed C-type lectin MGL. Immunobiology 220: 185–192.     

11. Sancho D, Reis SC (2013) Sensing of cell death by myeloid C-type lectin receptors. Curr Opin Immunol 25: 46–52.     

12. Chang SY, Kweon MN (2010) Langerin-expressing dendritic cells in gut-associated lymphoid tissues. Immunol Rev 234: 233–246.     

13. Ingeborg SO, Unger WWJ, Yvette VK (2011) C-type lectin receptors for tumor eradication: future directions. Cancers 3: 3169–3188.     

14. Zhang F, Ren S, Zuo Y (2014) DC-SIGN, DC-SIGNR and LSECtin: C-type lectins for infection. Int Rev Immunol 33: 54–66.     

15. Yan H, Kamiya T, Suabjakyong P, et al. (2015) Targeting C-type lectin receptors for cancer immunity. Front Immunol 6: 408–416. 

16. Dambuza IM, Brown GD (2015) C-type lectins in immunity: recent developments. Curr Opin Immunol 32: 21–27.     

17. Ding D, Yao Y, Zhang S, et al. (2017) C-type lectins facilitate tumor metastasis. Oncol Lett 13: 13–21. 

18. Andersen CBF, Moestrup SK (2014) How calcium makes endocytic receptors attractive. Trends Biochem Sci 39: 82–90.     

19. Eggensperger A, Tampé R (2015) The transporter associated with antigen processing: a key player in adaptive immunity. Biol Chem 396: 1059–1072. 

20. Rodriguez A, Regnault A, Kleijmeer M, et al. (1999) Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells. Nat Cell Biol 1: 362–368.     

21. Solheim JC (1999) Class I MHC molecules: assembly and antigen presentation. Immunol Rev 172: 11–19.     

22. Gil-Torregrosa BC, Lennon-Duménil AM, Kessler B, et al. (2004) Control of cross-presentation during dendritic cell maturation. Eur J Immunol 34: 398–407.     

23. Heath WR, Carbone FR (2001) Cross-presentation in viral immunity and self-tolerance. Nat Rev Immunol 1: 126–135.     

24. Joffre OP, Segura E, Savina A, et al. (2012) Cross-presentation by dendritic cells. Nat Rev Immunol 12: 557–569.     

25. McDonnell AM, Robinson BWS, Currie AJ (2010) Tumor antigen cross-presentation and the dendritic cell: where it all begins? Clin Dev Immunol 2010: 539519–539527. 

26. Bousso P, Robey E (2003) Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes. Nat Immunol 4: 579–585. 

27. Randolph GJ, Jakubzick C, Qu C (2008) Antigen presentation by monocytes and monocyte-derived cells. Curr Opin Immunol 20: 52–60.     

28. Leiri?o P, Fresno CD, Ardavín C (2012) Monocytes as effector cells: activated Ly-6C(high) mouse monocytes migrate to the lymph nodes through the lymph and cross-present antigens to CD8+ T cells. Eur J Immunol 42: 2042–2051.     

29. Raghavan M, Wijeyesakere SJ, Peters LR, et al. (2013) Calreticulin in the immune system: ins and outs. Trends Immunol 34: 13–21.     

30. Lv D, Shen Y, Peng Y, et al. (2015) Neuronal MHC class I expression is regulated by activity driven calcium signaling. PLoS One 10: e0135223–e0135238.     

31. Skov S (1999) Intracellular signal transduction mediated by ligation of MHC class I molecules. Tissue Antigens 51: 215–223. 

32. Blum JS, Wearsch PA, Cresswell P (2013) Pathways of antigen processing. Annu Rev Immunol 31: 443–473.     

33. Roche PA, Furuta K (2015) The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol 15: 203–216.     

34. Mueller SN (2017) Spreading the load: antigen transfer between migratory and lymph node-resident dendritic cells promotes T-cell priming. Eur J Immunol 47: 1798–1801.     

35. Parton RG, Joggerst B, Simons K (1994) Regulated internalization of caveolae. J Cell Biol 127: 1199–1215.     

36. Levine TP, Chain BM (1992) Endocytosis by antigen presenting cells: dendritic cells are as endocytically active as other antigen presenting cells. Proc Natl Acad Sci USA 89: 8342–8346.     

37. Hohn C, Lee SR, Pinchuk LM, et al. (2009) Zebrafish kidney phagocytes utilize macropinocytosis and Ca+-dependent endocytic mechanisms. PLoS One 4: e4314–e4323.     

38. Calmette J, Bertrand M, Vétillard M, et al. (2016) Glucocorticoid-induced leucine zipper protein controls macropinocytosis in dendritic cells. J Immunol 197: 4247–4256.     

39. Ayroldi E, Riccardi C (2009) Glucocorticoid-induced leucine zipper (GILZ): a new important mediator of glucocorticoid action. FASEB J 23: 3649–3658.     

40. Ronchetti S, Migliorati G, Riccardi C (2015) GILZ as a mediator of the anti-inflammatory effects of glucocorticoids. Front Endocrinol 6: 170–175. 

41. Canton J, Schlam D, Breuer C, et al. (2016) Calcium-sensing receptors signal constitutive macropinocytosis and facilitate the uptake of NOD2 ligands in macrophages. Nat Commun 7: 11284–11295.     

42. Redka DS, Gütschow M, Grinstein S, et al. (2017) Differential ability of pro-inflammatory and anti-inflammatory macrophages to perform macropinocytosis. Mol Biol Cell pii: mbc.E17-06-0419. 

43. Carafoli E, Krebs J (2016) Why calcium? How calcium became the best communicator. J Biol Chem 291: 20849–20857. 

44. Caroppo R, Gerbino A, Fistetto G, et al. (2004) Extracellular calcium acts as a "third messenger" to regulate enzyme and alkaline secretion. J Cell Biol 166: 111–119.     

45. Drickamer K (1988) Two distinct classes of carbohydrate-recognition domains in animal lectins. J Biol Chem 263: 9557–9560. 

46. Drickamer K (1996) Ca(2+)-dependent sugar recognition by animal lectins. Biochem Soc T 24: 146–150.     

47. Weis WI, Taylor ME, Drickamer K (1998) The C-type lectin superfamily in the immune system. Immunol Rev 163: 19–34.     

48. Drickamer K, Taylor ME (2015) Recent insights into structures and functions of C-type lectins in the immune system. Curr Opin Struc Biol 34: 26–34.     

49. van Vliet SJ, Saeland E, Van KY (2008) Sweet preferences of MGL: carbohydrate specificity and function. Trends Immunol 29: 83–90.     

50. Van DD, Stolk DA, Van RVD, et al. (2017) Targeting C-type lectin receptors: a high-carbohydrate diet for dendritic cells to improve cancer vaccines. J Leukocyte Biol 102: 1017–1034.     

51. Napoletano C, Zizzari IG, Rughetti A, et al. (2012) Targeting of macrophage galactose-type C-type lectin (MGL) induces DC signaling and activation. Eur J Immunol 42: 936–945.     

52. Engering A, Geijtenbeck TBH, van Vliet SJ, et al. (2002) The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. J Immunol 168: 2118–2126.     

53. Database of human proteins containing CTLDs. Available from: http://www.imperial.ac.uk/research/animallectins/ctld/mammals/humandata%20updated.html. 

54. Cummings RD, McEver RP (2017) Chapter 34: C-Type lectins, In: Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology 3rd Ed. Cold Spring Harbor Laboratory Press, 2015–2017. 

55. Sancho D, Reis SC (2012) Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu Rev Immunol 30: 491–529.     

56. Billadeau DD, Leibson PJ (2002) ITAMs versus ITIMs: striking a balance during cell regulation. J Clin Invest 109: 161–168.     

57. Ivashkiv LB (2009) Cross-regulation of signaling by ITAM-associated receptors. Nat Immunol 10: 340–347.     

58. Bezbradica JS, Rosenstein RK, DeMarco RA, et al. (2014) A role for the ITAM signaling module in specifying cytokine-receptor functions. Nat Immunol 15: 333–342.     

59. Pollitt AY, Poulter NS, Gitz E, et al. (2014) Syk and Src family kinases regulate C-type lectin receptor 2 (CLEC-2)-mediated clustering of podoplanin and platelet adhesion to lymphatic endothelial cells. J Biol Chem 289: 35695–35710.     

60. Unkeless JC, Jin J (1997) Inhibitory receptors, ITIM sequences and phosphatases. Curr Opin Immunol 9: 338–343.     

61. van Vliet SJ, Aarnoudse CA, Vc BDB, et al. (2007) MGL-mediated internalization and antigen presentation by dendritic cells: a role for tyrosine-5. Eur J Immunol 37: 2075–2081.     

62. Harris RL, Cw VDB, Bowen DJ (2012) ASGR1 and ASGR2, the genes that encode the asialoglycoprotein receptor (Ashwell Receptor), are expressed in peripheral blood monocytes and show inter-individual differences in transcript profile. Mol Biol Int 2012: 283974–283983. 

63. East L, Isacke CM (2002) The mannose receptor family. BBA-Gen Subjects 1572: 364–386.     

64. Uniport. Available from: http://www.uniprot.org/uniprot/P22897.

65. Lo YL, Liou GG, Lyu JH, et al. (2016) Dengue virus infection is through a cooperative interaction between a mannose receptor and CLEC5A on macrophage as a multivalent hetero-complex. PLoS One 11: e0166474–e0166486.     

66. R?dgaard-Hansen S, Rafique A, Christensen PA, et al. (2014) A soluble form of the macrophage-related mannose receptor (MR/CD206) is present in human serum and elevated in critical illness. Clin Chem Lab Med 52: 453–461. 

67. Feinberg H, Park-Snyder S, Kolatkar AR, et al. (2000) Structure of a C-type carbohydrate recognition domain from the macrophage mannose receptor. J Biol Chem 275: 21539–21548.    

68. Ng KKS, Park-Snyder S, Weis WI (1998) Ca2+-dependent structural changes in C-type mannose-binding proteins. Biochemistry 37: 17965–17976.     

69. Iobst ST, Wormald MR, Weis WI, et al. (1994) Binding of sugar ligands to Ca(2+)-dependent animal lectins. I. Analysis of mannose binding by site-directed mutagenesis and NMR. J Biol Chem 269: 15505–15511. 

70. Weis WI, Drickamer K, Hendrickson WA (1992) Structure of a C-type mannose-binding protein complexed with an oligosaccharide. Nature 360: 127–134.     

71. Drickamer K (1992) Engineering galactose-binding activity into a C-type mannose-binding protein. Nature 360: 183–186.     

72. Apostolopoulos V, Pietersz GA, Loveland, BE, et al. (1995) Oxidative/reductive conjugation of mannan to antigen selects for T1 or T2 immune responses. Proc Natl Acad Sci USA 92: 10128–10132.     

73. Apostolopoulos V, Pietersz GA, Gordon S, et al. (2000) Aldehyde-mannan antigen complexes target the MHC class I antigen-presentation pathway. Eur J Immunol 30: 1714–1723.    

74. Apostolopoulos V, Pietersz GA, Tsibanis A, et al. (2014) Dendritic cell immunotherapy: clinical outcomes. Clin Transl Immunol 3: e21–e24.     

75. Steinman RM, Turley S, Mellman I, et al. (2000) The induction of tolerance by dendritic cells that have captured apoptotic cells. J Exp Med 191: 411–416.     

76. Steinman RM, Hawiger D, Liu K, et al. (2003) Dendritic cell function in vivo during the steady state: a role in peripheral tolerance. Ann Ny Acad Sci 987: 15–25.     

77. Redmond WL, Sherman LA (2005) Peripheral tolerance of CD8 T lymphocytes. Immunity 22: 275–284.     

78. Chieppa M, Bianchi G, Doni A, et al. (2003) Cross-linking of the mannose receptor on monocyte-derived dendritic cells activates an anti-inflammatory immunosuppressive program. J Immunol 171: 4552–4560.     

79. Allavena P, Chieppa M, Blanchi G, et al. (2010) Engagement of the mannose receptor by tumoral mucins activates an immune suppressive phenotype in human tumor-associated macrophages. Clin Dev Immunol 2010: 547179–547188. 

80. Sharpe AH (2009) Mechanisms of costimulation. Immunol Rev 229: 5–11.     

81. Chen L, Flies DB (2013) Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol 13: 227–242.     

82. Anderson PJ, Kokame K, Sadler JE (2006) Zinc and calcium ions cooperatively modulate ADAMTS13 activity. J Biol Chem 281: 850–857.     

83. Sorvillo N, Pos W, Lm VDB, et al. (2017) The macrophage mannose receptor promotes uptake of ADAMTS13 by dendritic cells. Blood 119: 3828–3835. 

84. Mahnke K, Guo M, Lee S, et al. (2000) The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex class II-positive lysosomal compartments. J Cell Biol 151: 673–683.     

85. Platt CD, Ma JK, Chalouni C, et al. (2010) Mature dendritic cells use endocytic receptors to capture and present antigens. Proc Nat Acad Sci USA 107: 4287–4292.     

86. Tel J, Benitez-Ribas D, Hoosemans S, et al. (2011) DEC-205 mediates antigen uptake and presentation by both resting and activated human plasmacytoid dendritic cells. Eur J Immunol 41: 1014–1023.     

87. Hawiger D, Inaba K, Dorsett Y, et al. (2001) Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med 194: 769–779.     

88. Ma DY, Clark EA (2009) The role of CD40 and CD154/CD40L in dendritic cells. Semin Immunol 21: 265–272.     

89. Lee GH, Askari A, Malietzis G, et al. (2014) The role of CD40 expression in dendritic cell in cancer biology: a systematic review. Curr Cancer Drug Tar 14: 610–620.     

90. Sartorius R, D'Apice L, Trovato M, et al. (2015) Antigen delivery by filamentous bacteriophage fd displaying an anti-DEC-205 single-chain variable fragment confers adjuvanticity by triggering a TLR9-mediated immune response. Embo Mol Med 7: 973–988.     

91. Melander MC, Jürgensen HJ, Madsen DH, et al. (2015) The collagen receptor uPARAP/Endo180 in tissue degradation and cancer (Review). Int J Oncol 47: 1177–1188.     

92. Sturge J (2016) Endo180 at the cutting edge of bone cancer treatment and beyond. J Pathol 238: 485–488.     

93. Yuan C, Jürgensen HJ, Engelholm LH, et al. (2016) Crystal structures of the ligand-binding region of uPARAP: effect of calcium ion binding. Biochem J 473: 2359–2368.     

94. East L, Rushton S, Taylor ME, et al. (2002) Characterization of sugar binding by the mannose receptor family member, Endo180. J Biol Chem 277: 50469–50475.     

95. Augert A, Payré C, de Launoit Y, et al. (2009) The M-type receptor PLA2R regulates senescence through the p53 pathway. Embo Rep 10: 271–277.     

96. Jr BLH, Bonegio RG, Lambeau G, et al. (2009) M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. New Engl J Med 361: 11–21.     

97. Takahashi S, Watanabe K, Watanabe Y, et al. (2015) C-type lectin-like domain and fibronectin-like type II domain of phospholipase A2 receptor 1 modulate binding and migratory responses to collagen. Febs Lett 589: 829–835.     

98. Nolin JD, Ogden HL, Lai Y, et al. (2016) Identification of epithelial phospholipase A2 receptor 1 as a potential target in asthma. Am J Resp Cell Mol 55: 825–836.     

99. Fresquet M, Jowitt TA, McKenzie EA, et al. (2017) PLA2R binds to the annexin A2-S100A10 complex in human podocytes. Sci Rep 7: 6876–6886.     

100. Santamaria-Kisiel L, Rintala-Dempsey A, Shaw GS (2006) Calcium-dependent and -independent interactions of the S100 protein family. Biochem J 396: 201–214.     

101. Goder V, Spiess M (2001) Topogenesis of membrane proteins: determinants and dynamics. Febs Lett 504: 87–93.     

102. Zimmerman R, Eyrisch S, Ahmad M, et al. (2011) Protein translocation across the ER membrane. BBA-Biomembranes 1808: 912–924.     

103. Feinberg H, Mitchell DA, Drickamer K, et al. (2001) Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. Science 294: 2163–2166.    

104. Mitchell DA, Fadden AJ, Drickamer K (2001) A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands. J Biol Chem 276: 28939–28945. 

105. Guo Y, Feinberg H, Conroy E, et al. (2004) Structural basis for distinct ligand-binding and targeting properties of the receptors DC-SIGN and DC-SIGNR. Nat Struct Mol Biol 11: 591–598.     

106. Caparrós E, Munoz P, Sierra-Filardi E, et al. (2006) DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production. Blood 107: 3950–3958.    

107. Iyori M, Ohtani M, Hasebe A, et al. (2008) A role of the Ca2+ binding site of DC-SIGN in the phagocytosis of E. coli. Biochem Bioph Res Co 377: 367–372.     

108. Dos Santos á, Hadjivasiliou A, Ossa F, et al. (2017) Oligomerization domains in the glycan-binding receptors DC-SIGN and DC-SIGNR: sequence variation and stability differences. Protein Sci 26: 306–316.     

109. Dodagatta-Marri E, Mitchell DA, Pandit H, et al. (2017) Protein-protein interaction between surfactant protein D and DC-SIGN via C-type lectin domain can suppress HIV-1 transfer. Front Immunol 8: 834–845.     

110. Chao PZ, Hsieh MS, Cheng CW, et al. (2015) Dendritic cells respond to nasopharygeal carcinoma cells through annexin A2-recognizing DC-SIGN. Oncotarget 6: 159–170.     

111. Chia J, Goh G, Bard F (2016) Short O-GalNAc glycans: regulation and role in tumor development and clinical perspectives. BBA-Gen Subjects 1860: 1623–1639.     

112. Zheng J, Xiao H, Wu R (2017) Specific identification of glycoproteins bearing the Tn antigen in human cells. Angew Chem 129: 7213–7217.     

113. Feinberg H, Torgersen D, Drickamer K, et al. (2000) Mechanism of pH-dependent N-acetylgalactosamine binding by a functional mimic of the hepatocyte asialoglycoprotein receptor. J Biol Chem 275: 35176–35184.     

114. Morell AG, Gregoriadis G, Scheinberg IH, et al. (1971) The role of sialic acid in determining the survival of glycoproteins in the circulation. J Biol Chem 246: 1461–1467. 

115. Grewal PK (2010) The Ashwell-Morell receptor. Method Enzymol 479: 223–241.     

116. Weigel PH, Yik JHN (2002) Glycans as endocytosis signals: the cases of the asialoprotein and hyaluronan/chrondroitin sulfate receptors. BBA-Gen Subjects 1572: 341–363.     

117. Dixon LJ, Barnes M, Tang H, et al. (2013) Kupffer Cells in the Liver. Compr Physiol 3: 785–797. 

118. Tsuiji M, Fujimori M, Ohashi Y, et al. (2002) Molecular cloning and characterization of a novel mouse macrophage C-type lectin, mMGL2, which has a distinct carbohydrate specificity from mMGL1. J Biol Chem 277: 28892–28901.     

119. Kolatkar AR, Weis WI (1996) Structural basis of galactose recognition by C-type animal lectins. J Biol Chem 271: 6679–6685.     

120. Meier M, Bider MD, Malashkevich VN, et al. (2000) Crystal structure of the carbohydrate recognition domain of the H1 subunit of the asialoglycoprotein receptor. J Mol Biol 300: 857–865.     

121. Higashi N, Fujioka K, Denda-Nagai K, et al. (2002) The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte-derived immature dendritic cells. J Biol Chem 277: 20686–20693.    

122. Lundberg K, Rydnert F, Broos S, et al. (2016) C-type lectin receptor expression on human basophils and effects of allergen-specific immunotherapy. Scand J Immunol 84: 150–157.     

123. Vukman KV, Ravidà A, Aldridge AM, et al. (2013) Mannose receptor and macrophage galactose-type lectin are involved in Bordetella pertussis mast cell interaction. J Leukocyte Biol 94: 439–448.     

124. Savola P, Kelkka T, Rajala HL, et al. (2017) Somatic mutations in clonally expanded cytotoxic T lymphocytes in patients with newly diagnosed rheumatoid arthritis. Nat Commun 8: 15869–15882.     

125. Gaur P, Myles A, Misra R, et al. (2016) Intermediate monocytes are increased in enthesitis-related arthritis, a category of juvenile idiopathic arthritis. Clin Exp Immunol 187: 234–241. 

126. Vlismas A, Bletsa R, Mavrogianni D, et al. (2016) Microarray analyses reveal marked differences in growth factor and receptor expression between 8-cell human embryos and pluripotent stem cells. Stem Cells Dev 25: 160–177.     

127. Klimmeck D, Hanssong J, Raffel S, et al. (2012) Proteomic cornerstones of hematopoietic stem cell differentiation: distinct signatures of multipotent progenitors and myeloid committed cells. Molec Cell Proteomics 11: 286–302.     

128. Winkler C, Witte L, Moraw N, et al. (2014) Impact of endobronchial allergen provocation on macrophage phenotype in asthmatics. BMC Immunol 15: 12–22.    

129. Mathews JA, Kasahara DI, Ribeiro L, et al. (2015) γδ T cells are required for M2 macrophage polarization and resolution of ozone-induced pulmonary inflammation in mice. PLoS One 10: e0131236–e0131251.     

130. Shin H, Kumamoto Y, Gopinath S, et al. (2016) CD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2. Nat Commun 7: 13346–13355.     

131. Linehan JL, Dileepan T, Kashem SW, et al. (2015) Generation of Th17 cells in response to intranasal infection requires TGF-β1 from dendritic cells and IL-6 from CD301b+ dendritic cells. Proc Natl Acad Sci USA 112: 12782–12787. 132. Wong KL, Tai JJ, Wong WC, et al. (2011) Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood 118: e16–e31.     

133. Wong KL, Yeap WH, Tai JJY, et al. (2012) The three human monocyte subsets: implications for health and disease. Immunol Res 53: 41–57.     

134. Michlmayr D, Andrade P, Gonzalez K, et al. (2017) CD14+CD16+ monocytes are the main target of Zika virus infection in peripheral blood mononuclear cells in a paediatric study in Nicaragua. Nat Microbiol 2: 1462–1470.     

135. Knudsen NH, Lee CH (2016) Identity crisis: CD301b(+) mononuclear phagocytes blur the M1-M2 macrophage line. Immunity 45: 461–463.     

136. Zhang W, Xu W, Xiong S (2011) Macrophage differentiation and polarization via phosphatidylinositol 3-kinase/Akt-ERK signaling pathway conferred by serum amyloid P component. J Immunol 187: 1764–1777.     

137. Trowbridge IS, Thomas M (1994) CD45: an emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development. Annu Rev Immunol 12: 85–116.     

138. van Vliet SJ, Gringhuis SI, Geijtenbeek TBH, et al. (2006) Regulation of effector T cells by antigen-presenting cells via interaction with the C-type lectin MGL with CD45. Nat Immunol 11: 1200–1208. 

139. Nam HJ, Poy F, Saito H, et al. (2005) Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45. J Exp Med 201: 441–452.     

140. Xu Z, Weiss A (2002) Negative regulation of CD45 by differential homodimerization of the alternatively spliced isoforms. Nat Immunol 3: 764–771.     

141. Kumar V, Cheng P, Condamine T, et al. (2016) CD45 phosphatase inhibits STAT3 transcription factor activity in myeloid cells and promotes tumor-associated macrophage differentiation. Immunity 44: 303–315.     

142. van Vliet SJ, van Liempt E, Geijtenbeek TB, et al. (2006) Differential regulation of C-type lectin expression on tolerogenic dendritic cell subsets. Immunobiology 211: 577–585.     

143. Marcelo F, Garcia-Martin F, Matsushita T, et al. (2014) Delineating binding modes of Gal/GalNAc and structural elements of the molecular recognition of tumor-associated mucin glycopeptides by the human macrophage galactose-type lectin. Chem Eur J 20: 16147–16155.     

144. Tanaka J, Gleinich AS, Zhang Q, et al. (2017) Specific and differential binding of N-acetylgalactosamine glycopolymers to the human macrophage galactose lectin and asialoglycoprotein receptor. Biomacromolecules 18: 1624–1633.     

145. Khorev O, Stokmaier D, Schwardt O, et al. (2008) Trivalent, Gal/GaNAc-containing ligands designed for the asialoglycoprotein receptor. Bioorg Med Chem 16: 5216–5231.     

146. Nair JK, Willoughby JLS, Chan A, et al. (2014) Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J Am Chem Soc 136: 16958–16961.     

147. Lo-Man R, Bay S, Vichier-Guerre S, et al. (1999) A fully synthetic immunogen carrying a carcinoma-associated carbohydrate for active specific immunotherapy. Cancer Res 59: 1520–1524. 

148. Lo-Man R, Vichier-Guerre S, Bay S, et al. (2001) Anti-tumor immunity provided by a synthetic multiple antigenic glycopeptide displaying a tri-Tn glycotope. J Immunol 166: 2849–2854.     

149. Morgan AJ, Platt FM, Lloyd-Evans E, et al. (2011) Molecular mechanisms of endolysosomal Ca2+ signaling in health and disease. Biochem J 439: 349–374.     

150. Wragg S, Drickamer K (1999) Identification of amino acid residues that determine pH dependence of ligand binding to the asialoglyprotein receptor during endocytosis. J Biol Chem 274: 35400–35406.     

151. Onizuka T, Shimizu H, Moriwaki Y, et al. (2012) NMR study of ligand release from asialoglycoprotein receptor under solution conditions in early endosomes. Febs J 279: 2645–2656.     

152. Gerasimenko JV, Tepikin AV, Petersen OH, et al. (1998) Calcium uptake via endocytosis with rapid release from acidifying endosomes. Curr Biol 8: 1335–1338.     

153. Plattner H, Verkhratsky A (2016) Inseparable tandem: evolution chooses ATP and Ca2+ to control life, death and cellular signaling. Philos T R Soc B 371: 20150419–20150433.     

154. Napoletano C, Rughetti A, Tarp MPA, et al. (2007) Tumor-associated Tn-MUC1 glycoform is internalized through the macrophage galactose-type C-type lectin and delivered to the HLA class I and II compartments in dendritic cells. Cancer Res 67: 8358–8367.     

155. Hiltbold EM, Vlad AM, Ciborowski P, et al. (2000) The mechanism of unresponsiveness to circulating tumor antigen MUC1 is a block in intracellular sorting and processing by dendritic cells. J Immunol 165: 3730–3741.     

156. Hanisch FG, Schwientek T, Von BergweltBaildon MS, (2003) O-Linked glycans control glycoprotein processing by antigen-presenting cells: a biochemical approach to the molecular aspects of MUC1 processing by dendritic cells. Eur J Immunol 33: 3242–3254.     

157. Freire T, Zhang X, Dériaud E, et al. (2010) Glycosidic Tn-based vaccines targeting dermal dendritic cells favor germinal center B-cell development and potent antibody response in the absence of adjuvant. Blood 116: 3526–3536.     

158. Freire T, Lo-Man R, Bay S, et al. (2011) Tn glycosylation of the MUC6 protein modulates its immunogenicity and promotes the induction of the Th17-biased T cell responses. J Biol Chem 286: 7797–7811.     

159. Li D, Romain G, Flamar AL, et al. (2012) Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generate IL-10-producing suppressive CD4+ T cells. J Exp Med 209: 109–121.     

160. Valladeau J, Duvert-Frances V, Pin JJ, et al. (2001) Immature human dendritic cells express asialoglycoprotein receptor isoforms for efficient receptor-mediated endocytosis. J Immunol 167: 5767–5774.     

161. Garg S, Oran A, Wajchman J, et al. (2003) Genetic tagging shows increased frequency and longevity of antigen-presenting, skin-derived dendritic cells in vivo. Nat Immunol 4: 907–912.

162. Tomura M, Hata A, Matsuoka S, et al. (2014) Tracking and quantification of dendritic cell migration and antigen trafficking between the skin and lymph nodes. Sci Rep 4: 6030–6040. 

163. Kitano M, Yamazaki C, Takumi A, et al. (2016) Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node. Proc Natl Acad Sci USA 113: 1044–1049.     

164. Wan YY, Flavell RA (2009) How diverse-CD4 effector T cells and their functions. J Mol Cell Biol 1: 20–36.     

165. Lanzavecchia A (1985) Antigen-specific interaction between T and B cells. Nature 314: 537–539.     

166. Shumilina E, Huber SM, Lang F (2011) Ca2+ signaling in the regulation of dendritic cell functions. Am J Physiol Cell Ph 300: C1205–C1214.     

167. Cowen DS, Lazarus HM, Shurin SB, et al. (1989) Extracellular adenosine triphosphate activates calcium mobilization in human phagocytic leukocytes and neutrophil/monocyte progenitor cells. J Clin Invest 83: 1651–1660.     

168. Bretou M, Sáez PJ, Sanséau D, et al. (2017) Lysosome signaling controls the migration of dendritic cells. Sci Immunol 2: In press.

169. Vukcevic M, Zorzato F, Spagnoli G, et al. (2010) Frequent calcium oscillations lead to NFAT activation in human immature dendritic cells. J Biol Chem 285: 16003–16011.     

170. Jégouzo SAF, Quintero-Martinez, Ouyang X, et al. (2013) Organization of the extracellular portion of the macrophage galactose receptor: a trimeric cluster of simple binding sites for N-acetylgalactosamine. Glycobiology 23: 853–864.     

171. Humeau J, Bravo-San PJ, Vitale I, et al. (2017) Calcium signaling and cell cycle: progression or death. Cell Calcium 17: In press. 

172. Nicotera P, Orrenius S (1998) The role of calcium in apoptosis. Cell Calcium 23: 173–180.     

173. Schwarz EC, Qu B, Hoth M (013) Calcium, cancer and killing: the role of calcium in killing cancer cells by cytotoxic T lymphocytes and natural killing cells. BBA-Mol Cell Res 1833: 1603–1611. 

174. Cui C, Merritt R, Fu L, et al. (2017) Targeting calcium signaling in cancer therapy. Acta Pharm Sinica B 7: 3–17.     

175. Halling DB, Liebeskind BJ, Hall AW, et al. (2016) Conserved properties of individual Ca2+-binding sites in calmodulin. Proc Nat Acad Sci USA 113: E1216–E1225.     

176. Agrawal RS, Connolly SF, Herrmann TL, et al. (2007) MHC class II levels and intracellular localization in human dendritic cells are regulated by calmodulin kinase II. J Leukocyte Biol 82: 686–699.     

177. Connolly SF, Kusner DJ (2007) The regulation of dendritic cell function by calcium-signaling and its inhibition by microbial pathogens. Immunol Res 39: 115–127.     

178. Shi Y (2009) Serine/threonine phosphatases: mechanism through structure. Cell 139: 468–484.     

179. Song MS, Salmena L, Pandolfi PP (2012) The functions and regulation of the PTEN tumor suppressor. Nat Rev Mol Cell Bio 13: 283–296. 

180. Cho US, Xu W (2007) Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme. Nature 445: 53–57.     

181. Feske S (2007) Calcium signaling in lymphocyte activation and disease. Nat Rev Immunol 7: 690–702.     

182. Müller MR, Rao A (2010) NFAT, immunity and cancer: a transcription factor comes of age. Nat Rev Immunol 10: 645–656.     

183. Nakanishi A, Hatano N, Fujiwara Y, et al. (2017) AMP-activated protein-kinase-mediated feedback phosphorylation controls the Ca2+/calmodulin dependence of Ca2+/CaM-dependent protein kinase kinase β. J Biol Chem 292: 19804–19813.     

184. Gaertner TR, Kolodziej SJ, Wang D, et al. (2004) Comparative analysis of the three-dimensional structures and enzymatic properties of α, β, γ, and δ isoforms of Ca2+-calmodulin-dependent protein kinase II. J Biol Chem 279: 12484–12494.     

185. Wiede F, Dudakov JA, Lu KH, et al. (2017) PTPN2 regulates T cell lineage commitment and αβ versus γδ specification. J Exp Med 214: 2733–2758.     

186. Wang X, Marks CR, Perfitt TL, et al. (2017) A novel mechanism for Ca2+/calmodulin-dependent protein kinase II targeting to L-type Ca2+ channels that initiates long-range signaling to the nucleus. J Biol Chem 292: 17324–17336.     

187. Lin MY, Zal T, Ch'En IL, et al. (2005) A pivotal role for the multifunctional calcium/calmodulin-dependent protein kinase II in T cells: from activation to unresponsiveness. J Immunol 174: 5583–5592.     

188. Ratner AJ, Bryan R, Weber A, et al. (2017) Cystic fibrosis pathogens activate Ca2+-dependent mitogen-activated protein kinase signaling pathways in airway epithelial cells. J Biol Chem 276: 19267–19275. 

189. Bononi A, Agnoletto C, De ME, et al. (2011) Protein kinases and phosphatases in the control of cell fate. Enz Res 2011: 329098–329113. 

190. Suzuki K, Hata S, Kawabata Y, et al. (2004) Structure, activation, and biology of calpain. Diabetes 53: S12–S18.     

191. Frangioni JV, Oda A, Smith M, et al. (1993) Calpain-catalyzed cleavage and subcellular relocation of protein phosphotyrosine phosphatase 1B (PTP-1B) in human platelets. EMBO J 12: 4843–4856. 

192. Baba Y, Kurosaki T (2016) Role of calcium signaling in B cell activation and biology. Curr Top Microbiol 393: 143–147. 

193. Vaeth M, Zee I, Concepcion AR, et al. (2015) Ca2+ signaling but not store-operated Ca2+ entry is required for the function of macrophages and dendritic cells. J Immunol 195: 1202–1217.     

194. Ledderose C, Bao Y, Lidicky M, et al. (2014) Mitochondria are gate-keepers of T cell function by producing the ATP that drives purinergic signaling. J Biol Chem 289: 25936–25945.     

195. Zizzari IG, Napoletano C, Battisti F, et al. (2015) MGL receptor and immunity: when the ligand can make the difference. J Immunol Res 2015: 450695–450702. 

196. van Vliet SJ, Bay S, Vuist IM, et al. (2013) MGL signaling augments TLR2-mediated responses for enhanced IL-10 and TNF-α secretion. J Leukocyte Biol 94: 315–323.     

197. Nunes P, Demaurex N (2010) The role of calcium signaling in phagocytosis. J Leukocyte Biol 88: 57–68.     

198. Lm VDB, Gringhuis SI, Geijtenbeek TB (2012) An evolutionary perspective on C-type lectins in infection and immunity. Ann Ny Acad Sci 1253: 149–158.     

199. Kushchayev SV, Sankar T, Eggink LL, et al. (2012) Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part 1: stimulatory effects on blood monocytes and monocyte-derived cells of the brain. Cancer Manag Res 4: 309–323.

200. Kushchayev SV, Sankar T, Eggink LL, et al. (2012) Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part II: combination with external radiation improves survival. Cancer Manag Res 4: 325–334. 

201. Roby KF, Eggink LL, Hoober JK (2017) An innovative immunotherapeutic strategy for ovarian cancer: glycomimetic peptides [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017, Washington DC. Available from: http://cancerres.aacrjournals.org/content/77/13_Supplement/170.

Copyright Info: © 2017, J. Kenneth Hoober, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Article outline

Show full outline
Copyright © AIMS Press All Rights Reserved