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STAT1 signaling shields T cells from NK cell-mediated cytotoxicity.


ABSTRACT: The JAK-STAT pathway critically regulates T-cell differentiation, and STAT1 is postulated to regulate several immune-mediated diseases by inducing proinflammatory subsets. Here we show that STAT1 enables CD4+ T-cell-mediated intestinal inflammation by protecting them from natural killer (NK) cell-mediated elimination. Stat1-/- T cells fail to expand and establish colitis in lymphopenic mice. This defect is not fully recapitulated by the combinatorial loss of type I and II IFN signaling. Mechanistically, Stat1-/- T cells have reduced expression of Nlrc5 and multiple MHC class I molecules that serve to protect cells from NK cell-mediated killing. Consequently, the depletion of NK cells significantly rescues the survival and spontaneous proliferation of Stat1-/- T cells, and restores their ability to induce colitis in adoptive transfer mouse models. Stat1-/- mice however have normal CD4+ T cell numbers as innate STAT1 signaling is required for their elimination. Overall, our findings reveal a critical perspective on JAK-STAT1 signaling that might apply to multiple inflammatory diseases.

SUBMITTER: Kang YH 

PROVIDER: S-EPMC6385318 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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STAT1 signaling shields T cells from NK cell-mediated cytotoxicity.

Kang Yu Hui YH   Biswas Amlan A   Field Michael M   Snapper Scott B SB  

Nature communications 20190222 1


The JAK-STAT pathway critically regulates T-cell differentiation, and STAT1 is postulated to regulate several immune-mediated diseases by inducing proinflammatory subsets. Here we show that STAT1 enables CD4<sup>+</sup> T-cell-mediated intestinal inflammation by protecting them from natural killer (NK) cell-mediated elimination. Stat1<sup>-/-</sup> T cells fail to expand and establish colitis in lymphopenic mice. This defect is not fully recapitulated by the combinatorial loss of type I and II I  ...[more]

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