| First Author | Nakamura R | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 3 | Pages | 2071-5 |
| PubMed ID | 18641345 | Mgi Jnum | J:139234 |
| Mgi Id | MGI:3807596 | Doi | 10.4049/jimmunol.181.3.2071 |
| Citation | Nakamura R, et al. (2008) Tyk2-signaling plays an important role in host defense against Escherichia coli through IL-23-induced IL-17 production by gammadelta T cells. J Immunol 181(3):2071-5 |
| abstractText | Tyrosine kinase 2 (Tyk2), a member of the JAK-signal transducer family, is involved in intracellular signaling triggered by various cytokines, including IL-23. We have recently reported that resident gammadelta T cells in the peritoneal cavity of naive mice produced IL-17 in response to IL-23. In this study, we examined importance of Tyk2-mediated signaling in the IL-17 production by gammadelta T cells using Tyk2 deficient (-/-) mice. Gammadelta T cells in the peritoneal cavity of Tyk2(-/-) mice displayed effecter/memory phenotypes and TCR V repertoire similar to those in Tyk2(+/+) mice and produced comparable level of IL-17 to those in Tyk2(+/+) mice in response to PMA and ionomycin, indicating normal differentiation to IL-17-producing effectors in the absence of Tyk2-signaling. However, gammadelta T cells in Tyk2(-/-) mice produced less amount of IL-17 in response to IL-23 in vitro than those in Tyk2(+/+) mice. Similarly, gammadelta T cells in the peritoneal cavity of Tyk2(-/-) mice showed severely impaired IL-17 production after an i.p. infection with E. coli despite comparable level of IL-23 production to Tyk2(+/+) mice. As a consequence, Tyk2(-/-) mice showed a reduced infiltration of neutrophils and severely impaired bacterial clearance after Escherichia coli infection. These results indicate that Tyk2-signaling is critical for IL-23-induced IL-17 production by gammadelta T cells, which is involved in the first line of host defense by controlling neutrophil-mediated immune responses. |
