IL-33 acts as a costimulatory signal to generate alloreactive Th1 cells in graft-versus-host disease.

Détails

Ressource 1Télécharger: 35503257_BIB_9A7DBCB96AD9.pdf (7955.55 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_9A7DBCB96AD9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
IL-33 acts as a costimulatory signal to generate alloreactive Th1 cells in graft-versus-host disease.
Périodique
Journal of clinical investigation
Auteur⸱e⸱s
Dwyer G.K., Mathews L.R., Villegas J.A., Lucas A., Gonzalez de Peredo A., Blazar B.R., Girard J.P., Poholek A.C., Luther S.A., Shlomchik W., Turnquist H.R.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
15/06/2022
Peer-reviewed
Oui
Volume
132
Numéro
12
Pages
e150927
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Antigen-presenting cells (APCs) integrate signals emanating from local pathology and program appropriate T cell responses. In allogeneic hematopoietic stem cell transplantation (alloHCT), recipient conditioning releases damage-associated molecular patterns (DAMPs) that generate proinflammatory APCs that secrete IL-12, which is a driver of donor Th1 responses, causing graft-versus-host disease (GVHD). Nevertheless, other mechanisms exist to initiate alloreactive T cell responses, as recipients with disrupted DAMP signaling or lacking IL-12 develop GVHD. We established that tissue damage signals are perceived directly by donor CD4+ T cells and promoted T cell expansion and differentiation. Specifically, the fibroblastic reticular cell-derived DAMP IL-33 is increased by recipient conditioning and is critical for the initial activation, proliferation, and differentiation of alloreactive Th1 cells. IL-33 stimulation of CD4+ T cells was not required for lymphopenia-induced expansion, however. IL-33 promoted IL-12-independent expression of Tbet and generation of Th1 cells that infiltrated GVHD target tissues. Mechanistically, IL-33 augmented CD4+ T cell TCR-associated signaling pathways in response to alloantigen. This enhanced T cell expansion and Th1 polarization, but inhibited the expression of regulatory molecules such as IL-10 and Foxp3. These data establish an unappreciated role for IL-33 as a costimulatory signal for donor Th1 generation after alloHCT.
Mots-clé
Animals, Bone Marrow Transplantation/adverse effects, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation/adverse effects, Humans, Interleukin-12, Interleukin-33/genetics, Mice, Mice, Inbred BALB C, Th1 Cells/pathology, Bone marrow transplantation, Costimulation, Immunology, Th1 response, Transplantation
Pubmed
Web of science
Open Access
Oui
Création de la notice
16/05/2022 7:46
Dernière modification de la notice
23/01/2024 7:31
Données d'usage