Breakdown of immune homeostasis in the testis of mice lacking Tyro3, Axl and Mer receptor tyrosine kinases

Immunology and Cell Biology

Volumn 91, Issue 6, 2013, Pages 416-426

  Zhang, Yue ^a   Li, Nan ^a   Chen, Qiaoyuan ^a   Yan, Keqin ^a   Liu, Zhenghui ^a   Zhang, Xiaoyan ^a   Liu, Peng ^a   Chen, Yongmei ^a   Han, Daishu ^a  

^a INSTITUTE OF BASIC MEDICAL SCIENCES   (China)

Author keywords

immune homeostasis; inflammation; TAM receptors; testis

Indexed keywords

AXL TYROSINE KINASE RECEPTOR; IMMUNOGLOBULIN G ANTIBODY; INTERLEUKIN 1BETA; INTERLEUKIN 6; MER TYROSINE KINASE RECEPTOR; MONOCYTE CHEMOTACTIC PROTEIN 1; TUMOR NECROSIS FACTOR ALPHA; TYRO3 TYROSINE KINASE RECEPTOR; TYROSINE KINASE RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL CELL; APOPTOSIS; ARTICLE; BLOOD TESTIS BARRIER; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DEGENERATION; GERM CELL; HOMEOSTASIS; IMMUNE HOMEOSTASIS; IN VITRO STUDY; INFLAMMATION; LYMPHOCYTIC INFILTRATION; MACROPHAGE; MALE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; SEMINIFEROUS TUBULE EPITHELIUM; SERTOLI CELL; SEXUAL MATURITY; SPERMATOGENESIS; TESTIS; UPREGULATION;

ANIMALS; AUTOANTIBODIES; BLOOD-TESTIS BARRIER; CELL MOVEMENT; CELLS, CULTURED; CYTOKINES; HOMEOSTASIS; INFLAMMATION MEDIATORS; LYMPHOCYTES; MACROPHAGES; MALE; MICE; MICE, KNOCKOUT; PROTO-ONCOGENE PROTEINS; RECEPTOR PROTEIN-TYROSINE KINASES; SERTOLI CELLS; SPERMATOGENESIS; TESTIS; UP-REGULATION;

MUS;

EID: 84879839138     PISSN: 08189641     EISSN: 14401711     Source Type: Journal    
DOI: 10.1038/icb.2013.22     Document Type: Article

References (43)

1. Schuppe HC, Meinhardt A, Allam JP, Bergmann M, Weidner W, Haidl G. Chronic orchitis: a neglected cause of male infertility? Andrologia 2008; 40: 84-91. (Pubitemid 351379679)
2. Li N, Wang T, Han D. Structural, cellular and molecular aspects of immune privilege in the testis. Front Immunol 2012; 3: 152.
3. De Cesaris P, Filippini A, Cervelli C, Riccioli A, Muci S, Starace G et al. Immunosuppressive molecules produced by Sertoli cells cultured in vitro: biological effects on lymphocytes. Biochem Biophys Res Commun 1992; 186: 1639-1646. (Pubitemid 23189514)
4. Cheng CY, Mruk DD. The blood-testis barrier and its implications for male contraception. Pharmacol Rev 2012; 64: 16-64.
5. Mital P, Hinton BT, Dufour JM. The blood-testis and blood-epididymis barriers are more than just their tight junctions. Biol Reprod 2011; 84: 851-858.
6. Meng J, Greenlee AR, Taub CJ, Braun RE. Sertoli cell-specific deletion of the androgen receptor compromises testicular immune privilege in mice. Biol Reprod 2011; 85: 254-260.
7. Hafizi S, Dahlback B. Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev 2006; 17: 295-304. (Pubitemid 44038616)
8. Hafizi S, Dahlback B. Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily. FEBS J 2006; 273: 5231-5244. (Pubitemid 44772384)
9. Rothlin CV, Lemke G. TAM receptor signaling and autoimmune disease. Curr Opin Immunol 2010; 22: 740-746.
10. Lu Q, Gore M, Zhang Q, Camenisch T, Boast S, Casagranda F et al. Tyro-3 family receptors are essential regulators of mammalian spermatogenesis. Nature 1999; 398: 723-728. (Pubitemid 29197652)
11. Lu Q, Lemke G. Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science 2001; 293: 306-311. (Pubitemid 32694748)
12. Lemke G, Burstyn-Cohen T. TAM receptors and the clearance of apoptotic cells. Ann N Y Acad Sci 2010; 1209: 23-29.
13. Chen Y, Wang H, Qi N, Wu H, Xiong W, Ma J et al. Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice. Reproduction 2009; 138: 655-666.
14. Wang H, Chen Y, Ge Y, Ma P, Ma Q, Ma J et al. Immunoexpression of Tyro 3 family receptors-Tyro 3, Axl, and Mer - and their ligand Gas6 in postnatal developing mouse testis. J Histochem Cytochem 2005; 53: 1355-1364. (Pubitemid 41513067)
15. Xiong W, Chen Y, Wang H, Wu H, Lu Q, Han D. Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells. Reproduction 2008; 135: 77-87.
16. Nakanishi Y, Shiratsuchi A. Phagocytic removal of apoptotic spermatogenic cells by Sertoli cells: mechanisms and consequences. Biol Pharm Bull 2004; 27: 13-16. (Pubitemid 41656665)
17. Rothlin CV, Ghosh S, Zuniga EI, Oldstone MB, Lemke G. TAM receptors are pleiotropic inhibitors of the innate immune response. Cell 2007; 131: 1124-1136. (Pubitemid 350235020)
18. Hedger MP. Toll-like receptors and signalling in spermatogenesis and testicular responses to inflammation - a perspective. J Reprod Immunol 2011; 88: 130-141.
19. Bhushan S, Tchatalbachev S, Klug J, Fijak M, Pineau C, Chakraborty T et al. Uropathogenic Escherichia coli block MyD88-dependent and activate MyD88-independent signaling pathways in rat testicular cells. J Immunol 2008; 180: 5537-5547.
20. Riccioli A, Starace D, Galli R, Fuso A, Scarpa S, Palombi F et al. Sertoli cells initiate testicular innate immune responses through TLR activation. J Immunol 2006; 177: 7122-7130. (Pubitemid 44715080)
21. Wu H, Wang H, Xiong W, Chen S, Tang H, Han D. Expression patterns and functions of toll-like receptors in mouse sertoli cells. Endocrinology 2008; 149: 4402-4412.
22. Sun B, Qi N, Shang T, Wu H, Deng T, Han D. Sertoli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and mer receptors. Endocrinology 2010; 151: 2886-2897.
23. Zhang X, Wang T, Deng T, Xiong W, Lui P, Li N et al. Damaged spermatogenic cells induce inflammatory gene expression in mouse Sertoli cells through the activation of Toll-like receptors 2 and 4. Mol Cell Endocrinol 2013; 365: 162-173.
24. Rival C, Theas MS, Suescun MO, Jacobo P, Guazzone V, van Rooijen N et al. Functional and phenotypic characteristics of testicular macrophages in experimental autoimmune orchitis. J Pathol 2008; 215: 108-117. (Pubitemid 351786029)
25. Bryniarski K, Szczepanik M, Maresz K, Ptak M, Ptak W. Subpopulations of mouse testicular macrophages and their immunoregulatory function. Am J Reprod Immunol 2004; 52: 27-35. (Pubitemid 39023019)
26. Hume DA, Halpin D, Charlton H, Gordon S. The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80: macrophages of endocrine organs. Proc Natl Acad Sci USA 1984; 81: 4174-4177. (Pubitemid 14054543)
27. Yule TD, Montoya GD, Russell LD, Williams TM, Tung KS. Autoantigenic germ cells exist outside the blood testis barrier. J Immunol 1988; 141: 1161-1167.
28. Rival C, Lustig L, Iosub R, Guazzone VA, Schneider E, Meinhardt A et al. Identification of a dendritic cell population in normal testis and in chronically inflamed testis of rats with autoimmune orchitis. Cell Tissue Res 2006; 324: 311-318.
29. Johnson MH. The distribution of immunoglobulin and spermatozoal autoantigen in the genital tract of the male guinea pig: its relationship to autoallergic orchitis. Fertil Steril 1972; 23: 383-392.
30. Dulin JN, Moore ML, Gates KW, Queen JH, Grill RJ. Spinal cord injury causes sustained disruption of the blood-testis barrier in the rat. PLoS One 2011; 6: e16456.
31. Winnall WR, Muir JA, Hedger MP. Rat resident testicular macrophages have an alternatively activated phenotype and constitutively produce interleukin-10 in vitro. J Leukoc Biol 2011; 90: 133-143.
32. Qu N, Naito M, Terayama H, Hirai S, Li J, Ogawa Y et al. Developmental ontogeny of autoantigens associated with localized autoimmunity in murine testis and epididymis. J Reprod Immunol 2010; 87: 45-51.
33. Hedger MP. Macrophages and the immune responsiveness of the testis. J Reprod Immunol 2002; 57: 19-34. (Pubitemid 35245737)
34. Jacobo P, Guazzone VA, Jarazo-Dietrich S, Theas MS, Lustig L. Differential changes in CD4+ and CD8+ effector and regulatory T lymphocyte subsets in the testis of rats undergoing autoimmune orchitis. J Reprod Immunol 2009; 81: 44-54.
35. Lemke G, Rothlin CV. Immunobiology of the TAM receptors. Nat Rev Immunol 2008; 8: 327-336. (Pubitemid 351595219)
36. Nagata S, Hanayama R, Kawane K. Autoimmunity and the clearance of dead cells. Cell 2010; 140: 619-630.
37. Yu L, Wang L, Chen S. Endogenous toll-like receptor ligands and their biological significance. J Cell Mol Med 2010; 14: 2592-2603.
38. Pelletier RM, Yoon SR, Akpovi CD, Silvas E, Vitale ML. Defects in the regulatory clearance mechanisms favor the breakdown of self-tolerance during spontaneous autoimmune orchitis. Am J Physiol Regul Integr Comp Physiol 2009; 296: R743-R762.
39. Mital P, Kaur G, Dufour JM. Immunoprotective sertoli cells: making allogeneic and xenogeneic transplantation feasible. Reproduction 2010; 139: 495-504.
40. Wang H, Xiong W, Chen Y, Ma Q, Ma J, Ge Y et al. Evaluation on the phagocytosis of apoptotic spermatogenic cells by Sertoli cells in vitro through detecting lipid droplet formation by Oil Red O staining. Reproduction 2006; 132: 485-492.
41. Shiratsuchi A, Umeda M, Ohba Y, Nakanishi Y. Recognition of phosphatidylserine on the surface of apoptotic spermatogenic cells and subsequent phagocytosis by Sertoli cells of the rat. J Biol Chem 1997; 272: 2354-2358. (Pubitemid 27058522)
42. Sharpe RM, McKinnell C, Kivlin C, Fisher JS. Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction 2003; 125: 769-784. (Pubitemid 36722545)
43. Meng J, Holdcraft RW, Shima JE, Griswold MD, Braun RE. Androgens regulate the permeability of the blood-testis barrier. Proc Natl Acad Sci USA 2005; 102: 16696-16700. (Pubitemid 41688839)