NF-kappa B1 p105 regulates T cell homeostasis and prevents chronic inflammation.
J Immunol
; 182(5): 3131-8, 2009 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-19234210
ABSTRACT
Transcription factor NF-kappaB is regulated by a family of inhibitors, IkappaBs, as well as the NF-kappaB1 and NF-kappaB2 precursor proteins, p105 and p100. Although the different NF-kappaB inhibitors can all inhibit NF-kappaB in vitro, their physiological functions are incompletely understood. In this study, we demonstrate that p105 plays an important role in the regulation of T cell homeostasis and prevention of chronic inflammation. Mice lacking p105, but expressing the mature NF-kappaB1 p50, spontaneously develop intestinal inflammation with features of human inflammatory bowel disease. This inflammatory disorder occurs under specific pathogen-free conditions and critically involves T cells. Consistently, the p105-deficient mice have reduced frequency of naive T cells and increased frequency of memory/effector T cells in the peripheral lymphoid organs. Although p105 is dispensable for the production of immunosuppressive regulatory T cells, p105 deficiency renders CD4 T cells more resistant to Treg-mediated inhibition. We further show that the loss of p105 results in hyperproduction of Th17 subset of inflammatory T cells. Together, these findings suggest a critical role for NF-kappaB1 p105 in the regulation of T cell homeostasis and differentiation and the control of chronic inflammation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Mediadores da Inflamação
/
Subunidade p50 de NF-kappa B
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article