Influence of Testosterone on Inflammatory Response in Testicular Cells and Expression of Transcription Factor Foxp3 in T Cells.

Monika Fijak, Lara-Jil Damm, Jan-Per Wenzel, Ferial Aslani, Magdalena Walecki, Eva Wahle, Florian Eisel, Sudhanshu Bhushan, Holger Hackstein, Nelli Baal, Gerhard Schuler, Lutz Konrad, Amir Rafiq, Laura O'Hara, Lee B Smith, Andreas Meinhardt

Index: Am. J. Reprod. Immunol. 74 , 12-25, (2015)

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Abstract

Previous studies demonstrated a strong association between low androgen levels and reduced capacity to mount an inflammatory response. However, the mechanisms underlying these observations are largely not understood.Generation of CD4+CD25+Foxp3+ regulatory T cells in Leydig cell-conditioned media was determined by flow cytometry and ELISA. Influence of testosterone on cytokine response was measured in LPS-stimulated testicular macrophages, Sertoli and peritubular cells.Leydig cell-conditioned media dose-dependently stimulated expression of transcription factor Foxp3 and secretion of IL-10 in splenic CD4+ T cells, an effect abolished by addition of the anti-androgen flutamide. In isolated Sertoli and peritubular cells, testosterone pre-treatment suppressed the LPS-induced inflammatory response on TNF-α mRNA expression, while no effect was evident in testicular macrophages (TM).Androgens can influence the immune system under normal conditions by the generation and functional differentiation of regulatory T cells and in testicular inflammation by direct effect on Sertoli and peritubular cells.© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.