The IL-25-dependent tuft cell circuit driven by intestinal helminths requires macrophage migration inhibitory factor (MIF).
Journal
Mucosal immunology
ISSN: 1935-3456
Titre abrégé: Mucosal Immunol
Pays: United States
ID NLM: 101299742
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
08
04
2021
accepted:
10
02
2022
revised:
31
01
2022
pubmed:
16
3
2022
medline:
1
12
2022
entrez:
15
3
2022
Statut:
ppublish
Résumé
Macrophage migration inhibitory factor (MIF) is a key innate immune mediator with chemokine- and cytokine-like properties in the inflammatory pathway. While its actions on macrophages are well-studied, its effects on other cell types are less understood. Here we report that MIF is required for expansion of intestinal tuft cells during infection with the helminth Nippostrongylus brasiliensis. MIF-deficient mice show defective innate responses following infection, lacking intestinal epithelial tuft cell hyperplasia or upregulation of goblet cell RELMβ, and fail to expand eosinophil, type 2 innate lymphoid cell (ILC2) and macrophage (M2) populations. Similar effects were observed in MIF-sufficient wild-type mice given the MIF inhibitor 4-IPP. MIF had no direct effect on epithelial cells in organoid cultures, and MIF-deficient intestinal stem cells could generate tuft cells in vitro in the presence of type 2 cytokines. In vivo the lack of MIF could be fully compensated by administration of IL-25, restoring tuft cell differentiation and goblet cell expression of RELM-β, demonstrating its requirement upstream of the ILC2-tuft cell circuit. Both ILC2s and macrophages expressed the MIF receptor CXCR4, indicating that MIF may act as an essential co-factor on both cell types to activate responses to IL-25 in helminth infection.
Identifiants
pubmed: 35288645
doi: 10.1038/s41385-022-00496-w
pii: S1933-0219(22)01751-2
pmc: PMC9705247
doi:
Substances chimiques
Macrophage Migration-Inhibitory Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1243-1256Subventions
Organisme : Wellcome Trust
ID : 106122
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107490
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104111
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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