Influence of testosterone on inflammatory response in testicular cells and expression of transcription factor Foxp3 in T cells

M Fijak, LJ Damm, JP Wenzel, F Aslani… - American journal of …, 2015 - Wiley Online Library
M Fijak, LJ Damm, JP Wenzel, F Aslani, M Walecki, E Wahle, F Eisel, S Bhushan
American journal of reproductive immunology, 2015Wiley Online Library
Problem 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. Methods of study Generation of
CD 4+ CD 25+ 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. Results Leydig cell …
Problem
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.
Methods of study
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.
Results
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).
Conclusions
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.
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