| First Author | Ito K | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 8 | Pages | 3080-5 |
| PubMed ID | 24516133 | Mgi Jnum | J:206822 |
| Mgi Id | MGI:5553014 | Doi | 10.1073/pnas.1311022111 |
| Citation | Ito K, et al. (2014) Integrin alpha9 on lymphatic endothelial cells regulates lymphocyte egress. Proc Natl Acad Sci U S A 111(8):3080-5 |
| abstractText | 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, alpha9 integrin, which is closely associated with activated beta1 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 alpha9 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 alpha9 integrin-dependent manner without affecting S1P synthesis and/or degradation. Blockade of alpha9 integrin-mediated signaling reduced lymphocyte egress from dLNs in several models, including experimental autoimmune encephalomyelitis, where it improved clinical scores and pathology. Therefore, manipulating alpha9 integrin function may offer a therapeutic strategy for treating various inflammatory disorders. |
