Tyrosine kinase 2 plays critical roles in the pathogenic CD4 T cell responses for the development of experimental autoimmune encephalomyelitis

Akiko Oyamada, Hiori Ikebe, Momoe Itsumi, Hirokazu Saiwai, Seiji Okada, Kazuya Shimoda, Yoichiro Iwakura, Keiichi I. Nakayama, Yukihide Iwamoto, Yasunobu Yoshikai, Hisakata Yamada

研究成果: Contribution to journalArticle査読

41 被引用数 (Scopus)

抄録

Tyrosine kinase 2 (Tyk2), a member of the JAK family, is involved in IL-12- and IL-23-mediated signaling. In the present study, we examined the roles of Tyk2 in the development of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) by using Tyk2 knockout (KO) mice. In vitro differentiation of Th1 but not Th17 cells was severely impaired in Tyk2 KO CD4 T cells, although Tyk2 KO Th17 cells did not respond to IL-23. Tyk2 KO mice showed complete resistance against EAE with no infiltration of CD4 T cells in the spinal cord. Surprisingly, the number of MOG-specific Th17 cells in the periphery was comparable between KO and wild-type (WT) mice, whereas Th1 cells were greatly reduced in Tyk2 KO mice. Adoptive transfer of MOG-primed WT T cells induced EAE in Tyk2 KO recipients, indicating that Tyk2 in the environment was dispensable for the infiltration of effector T cells into the spinal cord. A reduced but significant number of Tyk2 KO T cells were detected in the spinal cord of mice with EAE, which had been reconstituted with bone marrow cells of WT and KO mice. Furthermore, MOG-immunized Tyk2 KO mice developed EAE after adoptive transfer of MOG-primed WT Th1 cells, which might trigger local inflammation that recruits Th17 cells. Taken together, these results indicate that Tyk2 is critically involved in the pathogenic CD4 T cell responses and thus could be a target molecule for the treatment of autoimmune diseases.

本文言語英語
ページ(範囲)7539-7546
ページ数8
ジャーナルJournal of Immunology
183
11
DOI
出版ステータス出版済み - 12 1 2009

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

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