SOCS-3 regulates onset and maintenance of TH2-mediated allergic responses

Yoh Ichi Seki, Hiromasa Inoue, Naoko Nagata, Katsuhiko Hayashi, Satoru Fukuyama, Koichiro Matsumoto, Okiru Komine, Shinjiro Hamano, Kunisuke Himeno, Kyoko Inagaki-Ohara, Nicholas Cacalano, Anne O'Garra, Tadahilo Oshida, Hirohisa Saito, James A. Johnston, Akihiko Yoshimura, Masato Kubo

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301 Citations (Scopus)

Abstract

Members of the suppressor of cytokine signaling (SOCS) family are involved in the pathogenesis of many inflammatory diseases. SOCS-3 is predominantly expressed in T-helper type 2 (TH2) cells, but its role in T H2-related allergic diseases remains to be investigated. In this study we provide a strong correlation between SOCS-3 expression and the pathology of asthma and atopic dermatitis, as well as serum IgE levels in allergic human patients. SOCS-3 transgenic mice showed increased TH2 responses and multiple pathological features characteristic of asthma in an airway hypersensitivity model system. In contrast, dominant-negative mutant SOCS-3 transgenic mice, as well as mice with a heterozygous deletion of Socs3, had decreased TH2 development. These data indicate that SOCS-3 has an important role in regulating the onset and maintenance of T H2-mediated allergic immune disease, and suggest that SOCS-3 may be a new therapeutic target for the development of antiallergic drugs.

Original languageEnglish
Pages (from-to)1047-1054
Number of pages8
JournalNature medicine
Volume9
Issue number8
DOIs
Publication statusPublished - 2003 Aug 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Seki, Y. I., Inoue, H., Nagata, N., Hayashi, K., Fukuyama, S., Matsumoto, K., Komine, O., Hamano, S., Himeno, K., Inagaki-Ohara, K., Cacalano, N., O'Garra, A., Oshida, T., Saito, H., Johnston, J. A., Yoshimura, A., & Kubo, M. (2003). SOCS-3 regulates onset and maintenance of TH2-mediated allergic responses. Nature medicine, 9(8), 1047-1054. https://doi.org/10.1038/nm896