Breakdown of immune homeostasis in the testis of mice lacking Tyro3, Axl and Mer receptor tyrosine kinases
- PMID: 23689306
- DOI: 10.1038/icb.2013.22
Breakdown of immune homeostasis in the testis of mice lacking Tyro3, Axl and Mer receptor tyrosine kinases
Abstract
Tyro3, Axl and Mer (TAM) receptor tyrosine kinases triple knockout (TAM(-/-)) mice are male infertile due to impaired spermatogenesis. However, the mechanism by which TAM receptors regulate spermatogenesis remains unclear. In this study, we demonstrate that the testicular immune homeostasis was impaired in TAM(-/-) mice. As development after the onset of sexual maturity, germ cells were progressively degenerated. Macrophages and lymphocytes infiltrated into the testis as TAM(-/-) mice aged. Moreover, the integrity of blood-testis barrier was impaired, and the autoantibodies against germ cell antigens were produced. Major inflammatory cytokines, including tumor necrosis factor-α, interleukin-6 and monocyte chemotactic protein 1 were upregulated in the testis of TAM(-/-) mice, and predominantly located in Sertoli cells (SCs). In vitro assays showed that TAM(-/-) SCs secrete significantly high levels of inflammatory cytokines compared with wild-type SCs after coculture with apoptotic germ cells. These results suggest that TAM receptors are important in the maintenance of the immune homeostasis in the testis.
Similar articles
-
Mice lacking Axl and Mer tyrosine kinase receptors are susceptible to experimental autoimmune orchitis induction.Immunol Cell Biol. 2015 Mar;93(3):311-20. doi: 10.1038/icb.2014.97. Epub 2014 Nov 18. Immunol Cell Biol. 2015. PMID: 25403570 Free PMC article.
-
Sertoli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and mer receptors.Endocrinology. 2010 Jun;151(6):2886-97. doi: 10.1210/en.2009-1498. Epub 2010 Apr 2. Endocrinology. 2010. PMID: 20363878
-
Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice.Reproduction. 2009 Oct;138(4):655-66. doi: 10.1530/REP-09-0101. Epub 2009 Jul 14. Reproduction. 2009. PMID: 19602523
-
TAM receptor tyrosine kinase function and the immunopathology of liver disease.Am J Physiol Gastrointest Liver Physiol. 2016 Jun 1;310(11):G899-905. doi: 10.1152/ajpgi.00382.2015. Epub 2016 Feb 11. Am J Physiol Gastrointest Liver Physiol. 2016. PMID: 26867565 Free PMC article. Review.
-
Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment.Mol Cancer. 2019 May 14;18(1):94. doi: 10.1186/s12943-019-1022-2. Mol Cancer. 2019. PMID: 31088471 Free PMC article. Review.
Cited by
-
The transcription factors NR5A1 and JUNB cooperate to activate the Axl promoter in mouse Sertoli cell lines.Mol Biol Rep. 2024 Sep 14;51(1):982. doi: 10.1007/s11033-024-09934-3. Mol Biol Rep. 2024. PMID: 39271559
-
Blood-testis barrier and spermatogenesis: lessons from genetically-modified mice.Asian J Androl. 2014 Jul-Aug;16(4):572-80. doi: 10.4103/1008-682X.125401. Asian J Androl. 2014. PMID: 24713828 Free PMC article. Review.
-
The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy.Cancers (Basel). 2016 Oct 21;8(10):97. doi: 10.3390/cancers8100097. Cancers (Basel). 2016. PMID: 27775650 Free PMC article. Review.
-
Physiological Roles of Apoptotic Cell Clearance: Beyond Immune Functions.Life (Basel). 2021 Oct 26;11(11):1141. doi: 10.3390/life11111141. Life (Basel). 2021. PMID: 34833017 Free PMC article. Review.
-
Mice lacking Axl and Mer tyrosine kinase receptors are susceptible to experimental autoimmune orchitis induction.Immunol Cell Biol. 2015 Mar;93(3):311-20. doi: 10.1038/icb.2014.97. Epub 2014 Nov 18. Immunol Cell Biol. 2015. PMID: 25403570 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
