ILC3s control splenic cDC homeostasis via lymphotoxin signaling.
Animals
Cell Adhesion Molecules
/ genetics
Dendritic Cells
/ immunology
Female
Immunity, Innate
Lymphoid Tissue
/ cytology
Lymphotoxin beta Receptor
/ genetics
Lymphotoxin-alpha
/ genetics
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Nuclear Receptor Subfamily 1, Group F, Member 3
/ genetics
Receptors, Immunologic
/ genetics
Signal Transduction
/ genetics
Spleen
/ cytology
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
03 05 2021
03 05 2021
Historique:
received:
09
05
2019
revised:
12
09
2020
accepted:
05
02
2021
entrez:
16
3
2021
pubmed:
17
3
2021
medline:
5
10
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33724364
pii: 211890
doi: 10.1084/jem.20190835
pmc: PMC7970251
pii:
doi:
Substances chimiques
Cell Adhesion Molecules
0
Esam protein, mouse
0
Lymphotoxin beta Receptor
0
Lymphotoxin-alpha
0
Nuclear Receptor Subfamily 1, Group F, Member 3
0
Ptpns1 protein, mouse
0
Receptors, Immunologic
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Research Council
ID : 789384
Pays : International
Organisme : European Research Council
ID : 851908
Pays : International
Organisme : NIAID NIH HHS
ID : R21 AI135574
Pays : United States
Informations de copyright
© 2021 Vanderkerken et al.
Déclaration de conflit d'intérêts
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.
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