ILC3s control splenic cDC homeostasis via lymphotoxin signaling.

Autor:	Vanderkerken M; Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Baptista AP; Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., De Giovanni M; Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA., Fukuyama S; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan., Browaeys R; Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium., Scott CL; Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB Center for Inflammation Research, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium., Norris PS; Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA., Eberl G; Institut Pasteur, Microenvironment and Immunity Unit, Paris, France.; Institut National de la Santé et de la Recherche Médicale U1224, Paris, France., Di Santo JP; Institut Pasteur, Innate Immunity Unit, Department of Immunology, Paris, France.; Institut National de la Santé et de la Recherche Médicale U1223, Paris, France., Vivier E; Innate Pharma Research Laboratories, Innate Pharma, Marseille, France.; Aix Marseille University, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d'Immunologie de Marseille-Luminy, Marseille, France.; Assistance Publique - Hôpitaux de Marseille, Hôpital de la Timone, Service d'Immunologie, Marseille-Immunopôle, Marseille, France., Saeys Y; Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium., Hammad H; Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Cyster JG; Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA., Ware CF; Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA., Tumanov AV; Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, TX., De Trez C; Laboratory of Cellular and Molecular Immunology, Vrij Universiteit Brussel, Brussels, Belgium., Lambrecht BN; Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.; Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2021 May 03; Vol. 218 (5).
DOI:	10.1084/jem.20190835
Abstrakt:	The spleen contains a myriad of conventional dendritic cell (cDC) subsets that protect against systemic pathogen dissemination by bridging antigen detection to the induction of adaptive immunity. How cDC subsets differentiate in the splenic environment is poorly understood. Here, we report that LTα1β2-expressing Rorgt+ ILC3s, together with B cells, control the splenic cDC niche size and the terminal differentiation of Sirpα+CD4+Esam+ cDC2s, independently of the microbiota and of bone marrow pre-cDC output. Whereas the size of the splenic cDC niche depended on lymphotoxin signaling only during a restricted time frame, the homeostasis of Sirpα+CD4+Esam+ cDC2s required continuous lymphotoxin input. This latter property made Sirpα+CD4+Esam+ cDC2s uniquely susceptible to pharmacological interventions with LTβR agonists and antagonists and to ILC reconstitution strategies. Together, our findings demonstrate that LTα1β2-expressing Rorgt+ ILC3s drive splenic cDC differentiation and highlight the critical role of ILC3s as perpetual regulators of lymphoid tissue homeostasis. Competing Interests: Disclosures:   E. Vivier is an employee of Innate Pharma. C.F. Ware reported grants from Capella Biosciences, grants from Eli Lilly, and grants from Boehringer Ingelheim Pharmaceuticals outside the submitted work; in addition, C.F. Ware had a patent to USP 8,974,787 issued and a patent to USP 8,349,320 issued. No other disclosures were reported. (© 2021 Vanderkerken et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu