STAT1 signaling shields T cells from NK cell-mediated cytotoxicity

Yu Hui Kang, Amlan Biswas, Michael Field and Scott B. Snapper ()
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Yu Hui Kang: Boston Children’s Hospital
Amlan Biswas: Boston Children’s Hospital
Michael Field: Boston Children’s Hospital
Scott B. Snapper: Boston Children’s Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08743-8

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