Characterization of the Micro-Environment of the Testis that Shapes the Phenotype and Function of Testicular Macrophages

表型 功能(生物学) 表征(材料科学) 细胞生物学 生物 材料科学 纳米技术 遗传学 基因
作者
Ming Wang,Monika Fijak,Hamid Hossain,Melanie Markmann,Rolf M. Nüsing,Günter Lochnit,Michaela F. Hartmann,Stefan A. Wudy,Lizong Zhang,Huanpeng Gu,Lutz Konrad,Trinad Chakraborty,Andreas Meinhardt,Sudhanshu Bhushan
出处
期刊:Journal of Immunology [American Association of Immunologists]
卷期号:198 (11): 4327-4340 被引量:100
标识
DOI:10.4049/jimmunol.1700162
摘要

Abstract Macrophages are important in the activation of innate immune responses and in a tissue-specific manner in the maintenance of organ homeostasis. Testicular macrophages (TM), which reside in the testicular interstitial space, comprise the largest leukocyte population in the testes and are assumed to play a relevant function in maintaining testicular immune privilege. Numerous studies have indicated that the interstitial fluid (IF) surrounding the TM has immunosuppressive properties, which may influence the phenotype of TM. However, the identity of the immunosuppressive molecules present in the IF is poorly characterized. We show that the rat testicular IF shifted GM-CSF–induced M1 toward the M2 macrophage phenotype. IF-polarized M2 macrophages mimic the properties of TM, such as increased expression of CD163, high secretion of IL-10, and low secretion of TNF-α. In addition, IF-polarized macrophages display immunoregulatory functions by inducing expansion of immunosuppressive regulatory T cells. We further found that corticosterone was the principal immunosuppressive molecule present in the IF and that the glucocorticoid receptor is needed for induction of the testis-specific phenotype of TM. In addition, TM locally produce small amounts of corticosterone, which suppresses the basal expression of inflammatory genes as a means to render TM refractory to inflammatory stimuli. Taken together, these results suggest that the corticosterone present in the testicular environment shapes the immunosuppressive function and phenotype of TM and that this steroid may play an important role in the establishment and sustenance of the immune privilege of the testis.
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