Tyk2-signaling plays an important role in host defense against Escherichia coli through IL-23-induced IL-17 production by γδ T cells

Risa Nakamura, Kensuke Shibata, Hisakata Yamada, Kazuya Shimoda, Keiichi Nakayama, Yasunobu Yoshikai

Research output: Contribution to journalArticle

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Abstract

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 γδ 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 γδ T cells using Tyk2 deficient (-/-) mice. γ 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, γδ T cells in Tyk2-/- mice produced less amount of IL-17 in response to IL-23 in vitro than those in Tyk2+/+ mice. Similarly, γδ 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 γδ T cells, which is involved in the first line of host defense by controlling neutrophil-mediated immune responses.

Original languageEnglish
Pages (from-to)2071-2075
Number of pages5
JournalJournal of Immunology
Volume181
Issue number3
Publication statusPublished - Aug 1 2008

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TYK2 Kinase
Interleukin-23
Interleukin-17
Escherichia coli
T-Lymphocytes
Peritoneal Cavity
Escherichia coli Infections
Mouse Tyk2 protein
Ionomycin
Neutrophil Infiltration
Transducers
Neutrophils
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Tyk2-signaling plays an important role in host defense against Escherichia coli through IL-23-induced IL-17 production by γδ T cells. / Nakamura, Risa; Shibata, Kensuke; Yamada, Hisakata; Shimoda, Kazuya; Nakayama, Keiichi; Yoshikai, Yasunobu.

In: Journal of Immunology, Vol. 181, No. 3, 01.08.2008, p. 2071-2075.

Research output: Contribution to journalArticle

Nakamura, Risa ; Shibata, Kensuke ; Yamada, Hisakata ; Shimoda, Kazuya ; Nakayama, Keiichi ; Yoshikai, Yasunobu. / Tyk2-signaling plays an important role in host defense against Escherichia coli through IL-23-induced IL-17 production by γδ T cells. In: Journal of Immunology. 2008 ; Vol. 181, No. 3. pp. 2071-2075.
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