Mast cell-derived IL-10 suppresses germinal center formation by affecting T follicular helper cell function.

Abstract

The most prevalent cancer diagnosed in the world is sunlight-induced skin cancer. In addition to being a complete carcinogen, UV radiation, the causative agent of skin cancer, induces immune suppression. Because UV-induced immune suppression is a well-recognized risk factor for skin cancer induction, it is crucial to understand the mechanisms underlying UV-induced immune suppression. Mast cells, which have recently emerged as immune regulatory cells, are particularly important in UV-induced immune suppression. UV exposure does not induce immune suppression in mast cell-deficient mice. We report that UV irradiation blocks germinal center (GC) formation, Ab secretion, and T follicular helper (Tfh) cell function, in part by altering the expression of transcription factors BCL-6 and BLIMP-1. No suppression of GC formation, Tfh cell IL-21 expression, or Ab secretion was observed in UV-irradiated mast cell-deficient (Kit(W-sh/W-sh)) mice. When mast cell-deficient mice were reconstituted with wild type mast cells, immune suppression was restored. Reconstituting the mast cell-deficient mice with bone marrow-derived mast cells from IL-10-deficient mice failed to restore the ability of UV radiation to suppress GC formation. Our findings demonstrate a function for mast cells, suppression of Tfh cell production, GC formation, and Ab production in vivo.

DOI: 10.4049/jimmunol.1001657

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@article{ChacnSalinas2011MastCI, title={Mast cell-derived IL-10 suppresses germinal center formation by affecting T follicular helper cell function.}, author={Rommel Chac{\'o}n-Salinas and Alberto Y Lim{\'o}n-Flores and Alma D Ch{\'a}vez-Blanco and Alexei Gonzalez-Estrada and Stephen E Ullrich}, journal={Journal of immunology}, year={2011}, volume={186 1}, pages={25-31} }