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Mucosal immunology

A safety catch to prevent intestinal inflammation

Nature Reviews Immunology volume 12, page 6 (2012)Cite this article

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In vitro assays have indicated that interleukin-6 (IL-6) — together with transforming growth factor-β — is a necessary differentiation factor for TH17 cells. However, the authors showed that memory T cells from the spleens of Il6−/− mice and wild-type mice secreted similar amounts of IL-17 and had similar levels of expression of the TH17 cell master regulator RORγt. By contrast, TH17 cell lineage commitment in the intestinal lamina propria was defective in Il6−/− mice, and this correlated with an increase in the number of TReg cells. These data indicate that IL-6 is required for TH17 cell differentiation in the intestines, but not in the spleen, and that this requirement might involve the balance between TH17 cells and TReg cells.

Adoptively transferred naive T cells expressing a dominant-negative form of the IL-6 receptor could differentiate into TH17 cells in the spleen and the liver but not in the lamina propria or the lungs. This indicates that IL-6 is a mucosal tissue-specific priming factor for TH17 cells. In support of this, oral bacterial infection of Il6−/− mice failed to generate TH17 cells in the mesenteric lymph nodes or the lamina propria, whereas intraperitoneal injection of bacteria leading to a systemic infection resulted in comparable TH17 cell priming in the spleen in Il6−/− and wild-type mice.

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ORIGINAL RESEARCH PAPER

  1. Hu, W. et al. Priming microenvironments dictate cytokine requirements for T helper 17 cell lineage commitment. Immunity 1 Dec 2011 (doi:10.1016/j.immuni.2011.10.013)

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  1. Kirsty Minton
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Minton, K. A safety catch to prevent intestinal inflammation. Nat Rev Immunol 12, 6 (2012). https://doi.org/10.1038/nri3144

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