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

Research output: Contribution to journalArticle

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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 - Aug 1 2003

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Maintenance
Cytokines
Transgenic Mice
Asthma
Anti-Allergic Agents
Th2 Cells
Immune System Diseases
Pathology
Atopic Dermatitis
Immunoglobulin E
Hypersensitivity
Serum
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

SOCS-3 regulates onset and maintenance of TH2-mediated allergic responses. / Seki, Yoh Ichi; Inoue, Hiromasa; Nagata, Naoko; Hayashi, Katsuhiko; Fukuyama, Satoru; Matsumoto, Koichiro; Komine, Okiru; Hamano, Shinjiro; Himeno, Kunisuke; Inagaki-Ohara, Kyoko; Cacalano, Nicholas; O'Garra, Anne; Oshida, Tadahilo; Saito, Hirohisa; Johnston, James A.; Yoshimura, Akihiko; Kubo, Masato.

In: Nature medicine, Vol. 9, No. 8, 01.08.2003, p. 1047-1054.

Research output: Contribution to journalArticle

Seki, YI, 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, JA, Yoshimura, A & Kubo, M 2003, 'SOCS-3 regulates onset and maintenance of TH2-mediated allergic responses', Nature medicine, vol. 9, no. 8, pp. 1047-1054. https://doi.org/10.1038/nm896
Seki, Yoh Ichi ; Inoue, Hiromasa ; Nagata, Naoko ; Hayashi, Katsuhiko ; Fukuyama, Satoru ; Matsumoto, Koichiro ; Komine, Okiru ; Hamano, Shinjiro ; Himeno, Kunisuke ; Inagaki-Ohara, Kyoko ; Cacalano, Nicholas ; O'Garra, Anne ; Oshida, Tadahilo ; Saito, Hirohisa ; Johnston, James A. ; Yoshimura, Akihiko ; Kubo, Masato. / SOCS-3 regulates onset and maintenance of TH2-mediated allergic responses. In: Nature medicine. 2003 ; Vol. 9, No. 8. pp. 1047-1054.
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