A role of suppressor of cytokine signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated interleukin 2 production

Akira Matsumoto, Yoh ichi Seki, Ryosuke Watanabe, Katsuhiko Hayashi, James A. Johnston, Yohsuke Harada, Ryo Abe, Akihiko Yoshimura, Masato Kubo

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Suppressor of cytokine signaling (SOCS)3 has been characterized as a negative feedback regulator in cytokine-mediated Janus kinase signal transducer and activator of transcription signaling. However, this study shows that T cells from transgenic mice expressing SOCS3 exhibit a significant reduction in interleukin (IL)-2 production induced by T cell receptor cross-linking when T cells are costimulated with CD28. Decreased protein expression in SOCS3+/- mice enhanced CD28-mediated IL-2 production, clearly indicating the correlation between expression level of SOCS3 and IL-2 production ability. The SOCS3 protein interacted with phosphorylated CD28 through its SH2 domain but not the kinase inhibitory region. In addition, a point mutation in the SOCS3 SH2 domain attenuated the inhibition of CD28 function in IL-2 promoter activation. Committed T helper (Th)2 cells exclusively expressed SOCS3 and production of Th2 cytokines, such as IL-4 and IL-5, was much less dependent on CD28 costimulation compared with interferon γ and IL-2 production in Th1 cells. Consistent with this notion, the expression level of SOCS3 in early T cell activation influenced the ability of IL-2 production induced by CD28 costimulation. Therefore, the SOCS3 may play an alternative role in prohibiting excessive progression of CD28-mediated IL-2 production.

Original languageEnglish
Pages (from-to)425-436
Number of pages12
JournalJournal of Experimental Medicine
Volume197
Issue number4
DOIs
Publication statusPublished - 2003 Feb 17
Externally publishedYes

Fingerprint

Interleukin-2
Cytokines
src Homology Domains
T-Lymphocytes
Janus Kinases
Th2 Cells
Th1 Cells
Interleukin-5
T-Cell Antigen Receptor
Transducers
Point Mutation
Interleukin-4
Interferons
Transgenic Mice
Phosphotransferases
Proteins

Keywords

  • CD28
  • Costimulation
  • IL-2 production
  • SOCS
  • T cell activation

ASJC Scopus subject areas

  • Immunology

Cite this

Matsumoto, A., Seki, Y. I., Watanabe, R., Hayashi, K., Johnston, J. A., Harada, Y., ... Kubo, M. (2003). A role of suppressor of cytokine signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated interleukin 2 production. Journal of Experimental Medicine, 197(4), 425-436. https://doi.org/10.1084/jem.20020939

A role of suppressor of cytokine signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated interleukin 2 production. / Matsumoto, Akira; Seki, Yoh ichi; Watanabe, Ryosuke; Hayashi, Katsuhiko; Johnston, James A.; Harada, Yohsuke; Abe, Ryo; Yoshimura, Akihiko; Kubo, Masato.

In: Journal of Experimental Medicine, Vol. 197, No. 4, 17.02.2003, p. 425-436.

Research output: Contribution to journalArticle

Matsumoto, A, Seki, YI, Watanabe, R, Hayashi, K, Johnston, JA, Harada, Y, Abe, R, Yoshimura, A & Kubo, M 2003, 'A role of suppressor of cytokine signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated interleukin 2 production', Journal of Experimental Medicine, vol. 197, no. 4, pp. 425-436. https://doi.org/10.1084/jem.20020939
Matsumoto, Akira ; Seki, Yoh ichi ; Watanabe, Ryosuke ; Hayashi, Katsuhiko ; Johnston, James A. ; Harada, Yohsuke ; Abe, Ryo ; Yoshimura, Akihiko ; Kubo, Masato. / A role of suppressor of cytokine signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated interleukin 2 production. In: Journal of Experimental Medicine. 2003 ; Vol. 197, No. 4. pp. 425-436.
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