| First Author | Rothhammer V | Year | 2011 |
| Journal | J Exp Med | Volume | 208 |
| Issue | 12 | Pages | 2465-76 |
| PubMed ID | 22025301 | Mgi Jnum | J:178760 |
| Mgi Id | MGI:5300102 | Doi | 10.1084/jem.20110434 |
| Citation | Rothhammer V, et al. (2011) Th17 lymphocytes traffic to the central nervous system independently of alpha4 integrin expression during EAE. J Exp Med 208(12):2465-76 |
| abstractText | The integrin alpha4beta1 (VLA-4) is used by encephalitogenic T cells to enter the central nervous system (CNS). However, both Th1 and Th17 cells are capable of inducing experimental autoimmune encephalomyelitis (EAE), and the molecular cues mediating the infiltration of Th1 versus Th17 cells into the CNS have not yet been defined. We investigated how blocking of alpha4 integrins affected trafficking of Th1 and Th17 cells into the CNS during EAE. Although antibody-mediated inhibition of alpha4 integrins prevented EAE when MOG(35-55)-specific Th1 cells were adoptively transferred, Th17 cells entered the brain, but not the spinal cord parenchyma, irrespective of alpha4 blockade. Accordingly, T cell-conditional alpha4-deficient mice were not resistant to actively induced EAE but showed an ataxic syndrome with predominantly supraspinal infiltrates of IL-23R(+)CCR6(+)CD4(+) T cells. The entry of alpha4-deficient Th17 cells into the CNS was abolished by blockade of LFA-1 (alphaLbeta2 integrin). Thus, Th1 cells preferentially infiltrate the spinal cord via an alpha4 integrin-mediated mechanism, whereas the entry of Th17 cells into the brain parenchyma occurs in the absence of alpha4 integrins but is dependent on the expression of alphaLbeta2. These observations have implications for the understanding of lesion localization, immunosurveillance, and drug design in multiple sclerosis. |
