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STAT1 signaling shields T cells from NK cell-mediated cytotoxicity

Author

Listed:
  • Yu Hui Kang

    (Boston Children’s Hospital
    Harvard Medical School)

  • Amlan Biswas

    (Boston Children’s Hospital
    Harvard Medical School
    Discovery Immunology, Abbvie)

  • Michael Field

    (Boston Children’s Hospital
    Harvard Medical School)

  • Scott B. Snapper

    (Boston Children’s Hospital
    Harvard Medical School)

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.

Suggested Citation

  • Yu Hui Kang & Amlan Biswas & Michael Field & Scott B. Snapper, 2019. "STAT1 signaling shields T cells from NK cell-mediated cytotoxicity," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08743-8
    DOI: 10.1038/s41467-019-08743-8
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