Lysophosphatidylserines derived from microbiota in Crohn's disease elicit pathological Th1 response.
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:
04 07 2022
04 07 2022
Historique:
received:
13
06
2021
revised:
17
03
2022
accepted:
02
05
2022
entrez:
24
5
2022
pubmed:
25
5
2022
medline:
27
5
2022
Statut:
ppublish
Résumé
Microbiota alteration and IFN-γ-producing CD4+ T cell overactivation are implicated in Crohn's disease (CD) pathogenesis. However, it remains unclear how dysbiosis enhances Th1 responses, leading to intestinal inflammation. Here, we identified key metabolites derived from dysbiotic microbiota that induce enhanced Th1 responses and exaggerate colitis in mouse models. Patients with CD showed elevated lysophosphatidylserine (LysoPS) concentration in their feces, accompanied by a higher relative abundance of microbiota possessing a gene encoding the phospholipid-hydrolyzing enzyme phospholipase A. LysoPS induced metabolic reprogramming, thereby eliciting aberrant effector responses in both human and mouse IFN-γ-producing CD4+ T cells. Administration of LysoPS into two mouse colitis models promoted large intestinal inflammation. LysoPS-induced aggravation of colitis was impaired in mice lacking P2ry10 and P2ry10b, and their CD4+ T cells were hyporesponsive to LysoPS. Thus, our findings elaborate on the mechanism by which metabolites elevated in patients with CD harboring dysbiotic microbiota promote Th1-mediated intestinal pathology.
Identifiants
pubmed: 35608941
pii: 213240
doi: 10.1084/jem.20211291
pmc: PMC9134096
pii:
doi:
Substances chimiques
Lysophospholipids
0
lysophosphatidylserine
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Core Research for Evolutional Science and TechnologyPRIME
Organisme : Japan Agency for Medical Research and Development
ID : 19gm1010004
Organisme : Osaka University Graduate School of Medicine
Organisme : Immunology Frontier Research Center
Organisme : Grant-in-Aid for Scientific Research
ID : 17H04159
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 Otake-Kasamoto et al.
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