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.
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.
Authors: Kenneth S K Tung; Jessica Harakal; Hui Qiao; Claudia Rival; Jonathan C H Li; Alberta G A Paul; Karen Wheeler; Patcharin Pramoonjago; Constance M Grafer; Wei Sun; Robert D Sampson; Elissa W P Wong; Prabhakara P Reddi; Umesh S Deshmukh; Daniel M Hardy; Huanghui Tang; C Yan Cheng; Erwin Goldberg Journal: J Clin Invest Date: 2017-02-20 Impact factor: 14.808
Authors: Tao Lei; Sandra M Blois; Nancy Freitag; Martin Bergmann; Sudhanshu Bhushan; Eva Wahle; Annie Chi-Chun Huang; Hung-Lin Chen; Michaela F Hartmann; Stefan A Wudy; Fu-Tong Liu; Andreas Meinhardt; Monika Fijak Journal: Cell Mol Life Sci Date: 2021-01-28 Impact factor: 9.261
Authors: Kate L Loveland; Britta Klein; Dana Pueschl; Sivanjah Indumathy; Martin Bergmann; Bruce E Loveland; Mark P Hedger; Hans-Christian Schuppe Journal: Front Endocrinol (Lausanne) Date: 2017-11-20 Impact factor: 5.555