AhR activation increases IL-2 production by alloreactive CD4+ T cells initiating the differentiation of mucosal-homing Tim3+ Lag3+ Tr1 cells.
Eur J Immunol
; 47(11): 1989-2001, 2017 11.
Article
en En
| MEDLINE
| ID: mdl-28833046
ABSTRACT
Activation of the aryl hydrocarbon receptor (AhR) by immunosuppressive ligands promotes the development of regulatory T (Treg) cells. Although AhR-induced Foxp3+ Treg cells have been well studied, much less is known about the development and fate of AhR-induced Type 1 Treg (AhR-Tr1) cells. In the current study, we identified the unique transcriptional and functional changes in murine CD4+ T cells that accompany the differentiation of AhR-Tr1 cells during the CD4+ T-cell-dependent phase of an allospecific cytotoxic T lymphocyte (allo-CTL) response. AhR activation increased the expression of genes involved in T-cell activation, immune regulation and chemotaxis, as well as a global downregulation of genes involved in cell cycling. Increased IL-2 production was responsible for the early AhR-Tr1 activation phenotype previously characterized as CD25+ CTLA4+ GITR+ on day 2. The AhR-Tr1 phenotype was further defined by the coexpression of the immunoregulatory receptors Lag3 and Tim3 and non-overlapping expression of CCR4 and CCR9. Consistent with the increased expression of CCR9, real-time imaging showed enhanced migration of AhR-Tr1 cells to the lamina propria of the small intestine and colon. The discovery of mucosal imprinting of AhR-Tr1 cells provides an additional mechanism by which therapeutic AhR ligands can control immunopathology.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
/
Interleucina-2
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Linfocitos T Reguladores
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Receptores de Hidrocarburo de Aril
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos