Involvement of RORγt-overexpressing T cells in the development of autoimmune arthritis in mice.
Arthritis Res Ther
; 17: 105, 2015 Apr 20.
Article
en En
| MEDLINE
| ID: mdl-25928901
ABSTRACT
INTRODUCTION:
Differentiation of T helper 17 cells is dependent on the expression of transcription retinoid-related orphan receptor gamma t (RORγt). The purpose of our study is to determine the role of RORγt expression in T cells on the development of collagen-induced arthritis (CIA).METHODS:
CIA was induced in C57BL/6 and T cell-specific RORγt transgenic (RORγt Tg) mice. At day 10 post-1st-immunization, lymph node (LN) cells were cultured with type II collagen (CII), and the expression levels of various cytokines and transcription factors on CD4+ T cells were measured. Total cells or CD4+ cells of draining LN were harvested from each mouse group after CII-immunization and transferred into C57BL/6 mice, and then CIA was induced in recipient mice. The expression levels of RORγt and other surface antigens, and the production of cytokines were analyzed in forkhead box P3 (Foxp3)+ regulatory T (Treg) cells. Foxp3+ Treg cells were analyzed for suppressive activity against proliferation of effector CD4+ T cells. Interlukin (IL)-10 neutralizing antibody was administrated in the course of CIA.RESULTS:
CIA was significantly suppressed in RORγt Tg mice compared with C57BL/6 mice. RORγt expression and IL-17 production were significantly higher in CII-reactive CD4+ T cells from RORγt Tg mice. Arthritis was significantly attenuated in C57BL/6 mice recipient of cells from RORγt Tg mice. Most of Foxp3+ Treg cells expressed RORγt, produced IL-10 but not IL-17, and overexpressed CC chemokine receptor 6 (CCR6) and surface antigens related to the suppressive activity of Foxp3+ Treg cells in RORγt Tg mice. In vitro suppression assay demonstrated significant augmentation of the suppressive capacity of Foxp3+ Treg cells in RORγt Tg mice. CIA was exacerbated in both C57BL/6 mice and RORγt Tg mice by the treatment of anti-IL-10 antibody.CONCLUSION:
Our results indicated that RORγt overexpression in T cells protected against the development of CIA. The protective effects were mediated, at least in part, through the anti-inflammatory effects including high production of IL-10 of RORγt+Foxp3+ Treg cells.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Artritis Experimental
/
Enfermedades Autoinmunes
/
ARN
/
Regulación de la Expresión Génica
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Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares
Límite:
Animals
Idioma:
En
Revista:
Arthritis Res Ther
Asunto de la revista:
REUMATOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Japón