Cutting edge: loss of α4 integrin expression differentially affects the homing of Th1 and Th17 cells

• Published in: The Journal of immunology (1950) Vol. 187; no. 12; pp. 6176 - 6179
• Main Authors: Glatigny, Simon, Duhen, Rebekka, Oukka, Mohamed, Bettelli, Estelle
• Format: Journal Article
• Language: English
• Published: United States 15.12.2011
• Subjects: Animals; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Migration Inhibition - genetics; Cell Migration Inhibition - immunology; Cells, Cultured; Encephalomyelitis, Autoimmune, Experimental - genetics; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Gene Deletion; Gene Expression Regulation - immunology; Integrin alpha4 - biosynthesis; Integrin alpha4 - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Th1 Cells - immunology; Th1 Cells - metabolism; Th1 Cells - pathology; Th17 Cells - immunology; Th17 Cells - metabolism; Th17 Cells - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1102515

The neutralization of α4 integrin is currently used as treatment in several autoimmune diseases and is thought to prevent the entry of most immune cells in target tissues. In this study, we showed that selective deletion of α4 integrin in T cells did not prevent but delayed the development of experimental autoimmune encephalomyelitis. Whereas both Th1 and Th17 cells infiltrate the CNS of wild-type mice, T cells present in the CNS of mice lacking α4 integrin were mainly enriched in Th17 cells, suggesting that this T cell subset uses other integrins to access the CNS. In contrast, α4 integrin expression is important for Th1 cells to enter the CNS and for the stability of their Th1-associated genetic program. Therefore, our data suggest that anti-α4 integrin Ab treatment may be more efficient in the treatment of Th1- rather than Th17-mediated disease.