Your browser doesn't support javascript.

Biblioteca Virtual em Saúde


Home > Pesquisa > ()
Imprimir Exportar

Formato de exportação:


Adicionar mais destinatários
| |

Integrin α9 on lymphatic endothelial cells regulates lymphocyte egress.

Ito, Koyu; Morimoto, Junko; Kihara, Akio; Matsui, Yutaka; Kurotaki, Daisuke; Kanayama, Masashi; Simmons, Szandor; Ishii, Masaru; Sheppard, Dean; Takaoka, Akinori; Uede, Toshimitsu.
Proc Natl Acad Sci U S A; 111(8): 3080-5, 2014 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-24516133
Sphingosine 1-phosphate (S1P) plays a role in lymphocyte egress from lymphoid organs. However, it remains unclear how S1P production and secretion are regulated. We show that under inflammatory conditions, α9 integrin, which is closely associated with activated ß1 integrin, and its ligand, tenascin-C, colocalize on medullary and cortical sinuses of draining lymph nodes (dLNs), which is a gate for lymphocyte exit, and that inhibition of lymphocyte egress is evident by blockade of α9 integrin-mediated signaling at dLNs. Based on in vitro analysis using lymphatic endothelial cells obtained from mice embryos, we suggested the possibility that stimulation of lymphatic endothelial cells by tenascin-C enhances S1P secretion in an α9 integrin-dependent manner without affecting S1P synthesis and/or degradation. Blockade of α9 integrin-mediated signaling reduced lymphocyte egress from dLNs in several models, including experimental autoimmune encephalomyelitis, where it improved clinical scores and pathology. Therefore, manipulating α9 integrin function may offer a therapeutic strategy for treating various inflammatory disorders.
Selo DaSilva