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

Zundler S, Becker E, Spocinska M, Slawik M, Parga-Vidal L, Stark R, Wiendl M, Atreya R, Rath T, Leppkes M, Hildner K, Lopez Posadas R, Lukassen S, Ekici AB, Neufert C, Atreya I, Van Gisbergen KPJM, Neurath M (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Nature Immunology Nature Research

Book Volume: 20

Pages Range: 288-+

Journal Issue: 3

DOI: 10.1038/s41590-018-0298-5

Abstract

Although tissue-resident memory T cells (T-RM 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 T-RM cells in human IBD and in experimental models of intestinal inflammation. Pro-inflammatory T-RM cells accumulated in the mucosa of patients with IBD, and the presence of CD4(+)CD69(+)CD103(+) T-RM cells was predictive of the development of flares. In vivo, functional impairment of T-RM cells in mice with double knockout of the T-RM-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 T-RM cells led to a suppression of colitis activity. Together, our data demonstrate a central role for T-RM cells in the pathogenesis of chronic intestinal inflammation and suggest that these cells could be targets for future therapeutic approaches in IBD.

Authors with CRIS profile

Sebastian Zundler Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Maximilian Wiendl Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Raja Atreya Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen (Heisenberg-Professur) Timo Rath Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Kai Hildner Juniorprofessur für Pneumologie/ Immunologie Rocío Lopez Posadas Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Sören Lukassen Professur für Humangenetik Arif Bülent Ekici Lehrstuhl für Humangenetik Clemens Neufert Medizinische Fakultät Markus Neurath Lehrstuhl für Innere Medizin I

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

IZKF-J63 (M1): The role of Interleukin-3 in experimental colitis and human inflammatory bowel disease Dec. 1, 2017 - Nov. 30, 2020

Involved external institutions

University of Amsterdam NL Netherlands (NL)

How to cite

APA:

Zundler, S., Becker, E., Spocinska, M., Slawik, M., Parga-Vidal, L., Stark, R.,... Neurath, M. (2019). Hobit- and Blimp-1-driven CD4(+) tissue-resident memory T cells control chronic intestinal inflammation. Nature Immunology, 20(3), 288-+. https://doi.org/10.1038/s41590-018-0298-5

MLA:

Zundler, Sebastian, et al. "Hobit- and Blimp-1-driven CD4(+) tissue-resident memory T cells control chronic intestinal inflammation." Nature Immunology 20.3 (2019): 288-+.

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