Altering the distribution of Foxp3(+) regulatory T cells results in tissue-specific inflammatory disease.
J Exp Med
; 204(6): 1335-47, 2007 Jun 11.
Article
em En
| MEDLINE
| ID: mdl-17548521
ABSTRACT
CD4(+)Foxp3(+) regulatory T cells (T reg) are essential for maintaining self-tolerance, but their functional mechanisms and sites of action in vivo are poorly defined. We examined the homing receptor expression and tissue distribution of T reg cells in the steady state and determined whether altering their distribution by removal of a single chemokine receptor impairs their ability to maintain tissue-specific peripheral tolerance. We found that T reg cells are distributed throughout all nonlymphoid tissues tested, and are particularly prevalent in the skin, where they express a unique CCR4(+)CD103(hi) phenotype. T reg cell expression of CCR4 and CD103 is induced by antigen-driven activation within subcutaneous lymph nodes, and accumulation of T reg cells in the skin and lung airways is impaired in the absence of CCR4 expression. Mice with a complete loss of CCR4 in the T reg cell compartment develop lymphocytic infiltration and severe inflammatory disease in the skin and lungs, accompanied by peripheral lymphadenopathy and increased differentiation of skin-tropic CD4(+)Foxp3(+) T cells. Thus, selectively altering T reg cell distribution in vivo leads to the development of tissue-specific inflammatory disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Reguladores
/
Tolerância a Antígenos Próprios
/
Fatores de Transcrição Forkhead
/
Inflamação
Limite:
Animals
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos