Spatial distribution of LTi-like cells in intestinal mucosa regulates type 3 innate immunity.

Autor:	Sécca C; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110., Bando JK; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305., Fachi JL; Laboratory of Immunoinflammation, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil.; Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., Gilfillan S; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110., Peng V; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110., Di Luccia B; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110., Cella M; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110., McDonald KG; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110., Newberry RD; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110., Colonna M; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; mcolonna@wustl.edu.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Jun 08; Vol. 118 (23).
DOI:	10.1073/pnas.2101668118
Abstrakt:	Lymphoid tissue inducer (LTi)-like cells are tissue resident innate lymphocytes that rapidly secrete cytokines that promote gut epithelial integrity and protect against extracellular bacterial infections.Here, we report that the retention of LTi-like cells in conventional solitary intestinal lymphoid tissue (SILT) is essential for controlling LTi-like cell function and is maintained by expression of the chemokine receptor CXCR5. Deletion of Cxcr5 functionally unleashed LTi-like cells in a cell intrinsic manner, leading to uncontrolled IL-17 and IL-22 production. The elevated production of IL-22 in Cxcr5 -deficient mice improved gut barrier integrity and protected mice during infection with the opportunistic pathogen Clostridium difficile Interestingly, Cxcr5 -/- mice developed LTi-like cell aggregates that were displaced from their typical niche at the intestinal crypt, and LTi-like cell hyperresponsiveness was associated with the local formation of this unconventional SILT. Thus, LTi-like cell positioning within mucosa controls their activity via niche-specific signals that temper cytokine production during homeostasis. Competing Interests: Competing interest statement: M. Colonna receives research support from Pfizer.
Databáze:	MEDLINE
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