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Hobit- and Blimp-1-driven CD4+ tissue-resident memory T cells control chronic intestinal inflammation.

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2019

Nat Immunol. 2019 Mar;20(3):288-300. doi: 10.1038/s41590-018-0298-5. Epub 2019 Jan 28.

Hobit- and Blimp-1-driven CD4+ tissue-resident memory T cells control chronic intestinal inflammation.

S Zundler;E Becker;M Spocinska;M Slawik;L Parga-Vidal;R Stark;M Wiendl;R Atreya;T Rath;M Leppkes;K Hildner;R López-Posadas;S Lukassen;AB Ekici;C Neufert;I Atreya;KPJM van Gisbergen;MF Neurath

Department of Medicine 1, Kussmaul Campus for Medical Research and Translational Research Center & Institute of Human Genetics, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany. Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory & Department of Experimental Immunology, Amsterdam UMC, The University of Amsterdam, Amsterdam, Netherlands.

Service type: Knock-in mice

Abstract

Although tissue-resident memory T cells (TRM cells) have been shown to regulate host protection in infectious disorders, their function in inflammatory bowel disease (IBD) remains to be investigated. Here we characterized TRM cells in human IBD and in experimental models of intestinal inflammation. Pro-inflammatory TRM cells accumulated in the mucosa of patients with IBD, and the presence of CD4+CD69+CD103+ TRM cells was predictive of the development of flares. In vivo, functional impairment of TRM cells in mice with double knockout of the TRM-cell-associated transcription factors Hobit and Blimp-1 attenuated disease in several models of colitis, due to impaired cross-talk between the adaptive and innate immune system. Finally, depletion of TRM cells led to a suppression of colitis activity. Together, our data demonstrate a central role for TRM cells in the pathogenesis of chronic intestinal inflammation and suggest that these cells could be targets for future therapeutic approaches in IBD.

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