Investigations on the direct involvement of TLRs in Th17 cells ar

Investigations on the direct involvement of TLRs in Th17 cells are vitally required in the near future. It has long been recognized that TLR ligands play an important indirect role in promoting T cell-mediated responses via their effects on innate immune cells, including up-regulating antigen presentation, co-stimulatory molecule expressions and inflammatory cytokine productions. It has become increasingly clear that TLR ligands can also act directly on T cells, possibly

as co-stimulatory molecules. In general, TLRs enhance effector T responses including cytokine production, proliferation and survival, while expanding the CD4+CD25+ PS-341 purchase Treg cell population with a transient loss of immunosuppressive function.

The molecular mechanisms for the TLR-mediated function in T cells and the direct effect of TLRs on Th17 cells need to be addressed in the future. More attention should be paid to the significance of the direct role of TLRs in T cells as, significantly, it will help us to understand fully the biological function of so-called innate receptors and develop more powerful adjuvants for controlling cellular immunity on purpose. The authors wish to thank Dr Zeqing Niu for his kind review of the manuscript. This work was supported by grants from the National Natural Science Foundation of China for Key Programs (C30630060 to Y. Z.), the National Natural Science Foundation Crizotinib concentration of China for General Program (C30972685 to G. L.), the grant from the Ministry of Science and Technology of China (2010CB945300) and the National Natural Science Foundation of China for Young Scientists (C30600567 to G. L.). The authors have no financial conflict of interest. “
“Myeloid-derived suppressor

cells (MDSCs) are present in most cancer patients and experimental animals where they exert a profound immune suppression and are a significant obstacle to immunotherapy. IFN-γ and IL-4 receptor alpha (IL-4Rα) have been implicated as essential molecules for MDSC development Adenosine triphosphate and immunosuppressive function. If IFN-γ and IL-4Rα are critical regulators of MDSCs, then they are potential targets for preventing MDSC accumulation or inhibiting MDSC function. Because data supporting a role for IFN-γ and IL-4Rα are not definitive, we have examined MDSCs induced in IFN-γ-deficient, IFN-γR-deficient, and IL-4Rα-deficient mice carrying three C57BL/6-derived (B16 melanoma, MC38 colon carcinoma, and 3LL lung adenocarcinoma), and three BALB/c-derived (4T1 and TS/A mammary carcinomas, and CT26 colon carcinoma) tumors. We report that although MDSCs express functional IFN-γR and IL-4Rα, and have the potential to signal through the STAT1 and STAT6 pathways, respectively, neither IFN-γ nor IL-4Rα impacts the phenotype, accumulation, or T-cell suppressive potency of MDSCs, although IFN-γ and IL-4Rα modestly alter MDSC-macrophage IL-10 crosstalk.

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