Immunology letters
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Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been implicated to have a functional role in immune response, mainly at concentrations commensurate with pregnancy. However, the underlying mechanisms remain to be fully understood. Here we present the evidences that progesterone inhibited immune response to lipopolysaccharide (LPS) and CpG oligodeoxynucleotides (CpG ODNs) through modulating Toll-like receptor (TLR) signaling. ⋯ Furthermore, we found that progesterone can significantly inhibit LPS-induced nitric oxide synthesis (iNOS), TLR4 expression and nuclear factor-kappaB (NF-kappaB) activation. Consistently, as a negative feedback inhibitor, the expression of suppressor of cytokine signaling (SOCS1) protein was up-regulated by progesterone in LPS-stimulated macrophages. These results support the concept that progesterone might inhibit innate immune response by suppressing NF-kappaB activation and enhancement of SOCS1 expression, providing a possible mechanistic explanation for the function of progesterone in regulating innate immune responses.
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Regulatory T cells (Tregs) expressing TCRalphabeta play a critical role in the maintenance of the immune system homeostasis. Tregs express the cell surface markers CD4 and CD25 as well as the transcription factor Foxp3. Foxp3(+)CD4(+)CD25(+)TCRalphabeta(+) Tregs can be generated from mouse and human CD4(+)CD25(-) T cells in vitro via TGF-beta induction. ⋯ Furthermore, the TGF-beta induced gammadelta T cells mediated a potent immunosuppressive effect on anti-CD3 stimulated T cell activation and proliferation. In contrast, although a small fraction of human peripheral blood and tumor infiltrating gammadelta T cells expressed Foxp3, similar culture condition with anti-TCRgammadelta plus TGF-beta failed to generate functional human Foxp3(+) gammadelta T cells. In conclusion, our results suggest that mouse splenic Foxp3(+) gammadelta T cells with suppressive function can be induced by TCR and TGF-beta costimulation, whereas functional human Foxp3(+) gammadelta T cells in peripheral blood could not be generated under the same condition.