ILC3s control splenic cDC homeostasis via lymphotoxin signaling

Matthias Vanderkerken, Antonio P. Baptista*, Marco De Giovanni, Satoshi Fukuyama, Robin Browaeys, Charlotte L. Scott, Paula S. Norris, Gerard Eberl, James P. Di Santo, Eric Vivier, Yvan Saeys, Hamida Hammad, Jason G. Cyster, Carl F. Ware, Alexei V. Tumanov, Carl De Trez, Bart N. Lambrecht

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Article numbere20190835
JournalJournal of Experimental Medicine
Volume218
Issue number5
DOIs
Publication statusPublished - 3 May 2021

Bibliographical note

Acknowledgments:
supported by a Marie-Sklodowska Curie Action fellowship as part of Horizon 2020; C.L. Scott is supported by the Fonds Wetenschappelijk Onderzoek Vlaanderen and a European Research Council starting grant; Y. Saeys is supported by the Fonds Wetenschappelijk Onderzoek Vlaanderen and the Marylou Ingram Scholar program; H. Hammad is supported by a research initiative grant from Ghent University; A.V. Tumanov is supported by grants from the National Institutes of Health (AI135574) and the Max and Minnie Tomerlin Voelcker Fund; and B.N. Lambrecht is supported by a European Research Council advanced grant, a research initiative grant from Ghent University, and an Excellence of Science research grant.

Publisher Copyright: © 2021 Rockefeller University Press. All rights reserved.

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