Donor Treg expansion by liposomal α-galactosylceramide modulates Tfh cells and prevents sclerodermatous chronic graft-versus-host disease.
Tfh cells
chronic graft-versus-host disease
hematopoietic stem cell transplantation
iNKT cells
regulatory T cells
α-galactosylceramide
Journal
Immunity, inflammation and disease
ISSN: 2050-4527
Titre abrégé: Immun Inflamm Dis
Pays: England
ID NLM: 101635460
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
14
02
2021
received:
29
04
2020
accepted:
15
03
2021
pubmed:
5
5
2021
medline:
16
10
2021
entrez:
4
5
2021
Statut:
ppublish
Résumé
Chronic graft-versus-host disease (cGVHD) is a major cause of nonrelapse morbidity and mortality following hematopoietic stem cell transplantation (HSCT). α-Galactosylceramide (α-GC) is a synthetic glycolipid that is recognized by the invariant T-cell receptor of invariant natural killer T (iNKT) cells in a CD1d-restricted manner. Stimulation of iNKT cells by α-GC leads to the production of not only immune-stimulatory cytokines but also immune-regulatory cytokines followed by regulatory T-cell (Treg) expansion in vivo. We investigated the effect of iNKT stimulation by liposomal α-GC just after transplant on the subsequent immune reconstitution and the development of sclerodermatous cGVHD. Our study showed that multiple administrations of liposomal α-GC modulated both host- and donor-derived iNKT cell homeostasis and induced an early expansion of donor Tregs. We also demonstrated that the immune modulation of the acute phase was followed by the decreased levels of CXCL13 in plasma and follicular helper T cells in lymph nodes, which inhibited germinal center formation, resulting in the efficient prevention of sclerodermatous cGVHD. These data demonstrated an important coordination of T- and B-cell immunity in the pathogenesis of cGVHD and may provide a novel clinical strategy for the induction of immune tolerance after allogeneic HSCT.
Sections du résumé
BACKGROUND AND AIM
Chronic graft-versus-host disease (cGVHD) is a major cause of nonrelapse morbidity and mortality following hematopoietic stem cell transplantation (HSCT). α-Galactosylceramide (α-GC) is a synthetic glycolipid that is recognized by the invariant T-cell receptor of invariant natural killer T (iNKT) cells in a CD1d-restricted manner. Stimulation of iNKT cells by α-GC leads to the production of not only immune-stimulatory cytokines but also immune-regulatory cytokines followed by regulatory T-cell (Treg) expansion in vivo.
METHODS
We investigated the effect of iNKT stimulation by liposomal α-GC just after transplant on the subsequent immune reconstitution and the development of sclerodermatous cGVHD.
RESULTS
Our study showed that multiple administrations of liposomal α-GC modulated both host- and donor-derived iNKT cell homeostasis and induced an early expansion of donor Tregs. We also demonstrated that the immune modulation of the acute phase was followed by the decreased levels of CXCL13 in plasma and follicular helper T cells in lymph nodes, which inhibited germinal center formation, resulting in the efficient prevention of sclerodermatous cGVHD.
CONCLUSIONS
These data demonstrated an important coordination of T- and B-cell immunity in the pathogenesis of cGVHD and may provide a novel clinical strategy for the induction of immune tolerance after allogeneic HSCT.
Identifiants
pubmed: 33942544
doi: 10.1002/iid3.425
pmc: PMC8342231
doi:
Substances chimiques
Galactosylceramides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
721-733Informations de copyright
© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.
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