@article{2d11fce2bdfb465aa58cfe15f8c82aeb,
title = "Spatial distribution of LTi-like cells in intestinal mucosa regulates type 3 innate immunity",
abstract = "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.",
keywords = "CXCR5, Innate lymphoid cells, Intestine, Lymphoid tissue, Mucosal immunity",
author = "Cristiane S{\'e}cca and Bando, {Jennifer K.} and Fachi, {Jos{\'e} L.} and Susan Gilfillan and Vincent Peng and Luccia, {Blanda Di} and Marina Cella and McDonald, {Keely G.} and Newberry, {Rodney D.} and Marco Colonna",
note = "Funding Information: ACKNOWLEDGMENTS. We would like to thank Erica Lantelme, Dorian Brinja, and Pascaline Akitani for assistance using cell sorters. We also thank Simone Brioschi for providing technical expertise in immunofluorescence staining of tissue sections and Genentech for kindly providing the anti-IL-22 antibody used in this study. We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by National Cancer Institute (NCI) Cancer Center Support Grant P30 CA91842 to the Siteman Cancer Center and by Institute for Clinical and Translational Sciences (ICTS) Clinical and Translational Sciences Award (CTSA) Grant UL1TR002345 from the National Center for Research Resources (NCRR), a component of the NIH, and NIH Roadmap for Medical Research. This publication is solely our responsibility and does not necessarily represent the official view of NCRR or NIH. This work was funded by NIH Grants U01 AI095542 (to M. Colonna), R01 DE025884 (to M. Colonna), R01 DK124699 (to M. Colonna), K99 DK118110 (to J.K.B.), F30 DK127540-01 (to V.P.), and T32 DK 77653-28 (to V.P.). M. Colonna receives research support from Pfizer. Funding Information: We would like to thank Erica Lantelme, Dorian Brinja, and Pascaline Akitani for assistance using cell sorters. We also thank Simone Brioschi for providing technical expertise in immunofluorescence staining of tissue sections and Genentech for kindly providing the anti-IL-22 antibody used in this study. We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by National Cancer Institute (NCI) Cancer Center Support Grant P30 CA91842 to the Siteman Cancer Center and by Institute for Clinical and Translational Sciences (ICTS) Clinical and Translational Sciences Award (CTSA) Grant UL1TR002345 from the National Center for Research Resources (NCRR), a component of the NIH, and NIH Roadmap for Medical Research. This publication is solely our responsibility and does not necessarily represent the official view of NCRR or NIH. This work was funded by NIH Grants U01 AI095542 (to M. Colonna), R01 DE025884 (to M. Colonna), R01 DK124699 (to M. Colonna), K99 DK118110 (to J.K.B.), F30 DK127540-01 (to V.P.), and T32 DK 77653-28 (to V.P.). M. Colonna receives research support from Pfizer. Publisher Copyright: {\textcopyright} 2021 National Academy of Sciences. All rights reserved.",
year = "2021",
month = jun,
day = "8",
doi = "10.1073/pnas.2101668118",
language = "English",
volume = "118",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "23",
}