Research ArticleMUCOSAL IMMUNOLOGY

T cell–derived interferon-γ programs stem cell death in immune-mediated intestinal damage

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Science Immunology  06 Dec 2019:
Vol. 4, Issue 42, eaay8556
DOI: 10.1126/sciimmunol.aay8556

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Protecting intestinal stem cells

As the intestinal epithelium is replaced every week, maintenance of this tissue requires rapid self-renewal that is driven by intestinal stem cells. This homeostasis is disrupted in a number of settings, including allogeneic bone marrow transplantation. After allogeneic bone marrow transplantation, allogeneic T cells often attack and kill intestinal cells in an interferon-γ (IFNγ)–dependent manner. Here, Takashima et al. have used both in vivo transplant models and in vitro organoid systems to define the targets of IFNγ in the intestine, and they found that IFNγ directly targets intestinal stem cells. They further demonstrate that JAK/STAT inhibitors can be used to protect the intestinal stem cell compartment from T cell–mediated damage in this setting. See the related Focus by Kretzschmar and Clevers.

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