Fibroblastic niches prime T cell alloimmunity through Delta-like Notch ligands.

Détails

Ressource 1Télécharger: JCI89535.pdf (5176.61 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_7C9AA9DC3589
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Fibroblastic niches prime T cell alloimmunity through Delta-like Notch ligands.
Périodique
Journal of Clinical Investigation
Auteur(s)
Chung J., Ebens C.L., Perkey E., Radojcic V., Koch U., Scarpellino L., Tong A., Allen F., Wood S., Feng J., Friedman A., Granadier D., Tran I.T., Chai Q., Onder L., Yan M., Reddy P., Blazar B.R., Huang A.Y., Brennan T.V., Bishop D.K., Ludewig B., Siebel C.W., Radtke F., Luther S.A., Maillard I.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
127
Numéro
4
Pages
1574-1588
Langue
anglais
Résumé
Alloimmune T cell responses induce graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (allo-BMT). Although Notch signaling mediated by Delta-like 1/4 (DLL1/4) Notch ligands has emerged as a major regulator of GVHD pathogenesis, little is known about the timing of essential Notch signals and the cellular source of Notch ligands after allo-BMT. Here, we have shown that critical DLL1/4-mediated Notch signals are delivered to donor T cells during a short 48-hour window after transplantation in a mouse allo-BMT model. Stromal, but not hematopoietic, cells were the essential source of Notch ligands during in vivo priming of alloreactive T cells. GVHD could be prevented by selective inactivation of Dll1 and Dll4 in subsets of fibroblastic stromal cells that were derived from chemokine Ccl19-expressing host cells, including fibroblastic reticular cells and follicular dendritic cells. However, neither T cell recruitment into secondary lymphoid organs nor initial T cell activation was affected by Dll1/4 loss. Thus, we have uncovered a pathogenic function for fibroblastic stromal cells in alloimmune reactivity that can be dissociated from their homeostatic functions. Our results reveal what we believe to be a previously unrecognized Notch-mediated immunopathogenic role for stromal cell niches in secondary lymphoid organs after allo-BMT and define a framework of early cellular and molecular interactions that regulate T cell alloimmunity.

Pubmed
Web of science
Open Access
Oui
Création de la notice
17/04/2017 16:20
Dernière modification de la notice
20/08/2019 14:38
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