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

Nature Medicine volume 9, pages 1047–1054 (2003)Cite this article

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 TH2-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 TH2-mediated allergic immune disease, and suggest that SOCS-3 may be a new therapeutic target for the development of antiallergic drugs.

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Figure 1: Selective expression of SOCS-3 in mouse and human TH2 cells.
Figure 2: Expression of SOCS-3 in asthma and atopic dermatitis patients.
Figure 3: Constitutive expression of SOCS-3 enhances the TH2 response in SOCS-3 transgenic mice.
Figure 4: Effects of constitutive expression of SOCS-3 in T cells on asthmatic responses in an OVA-induced asthma model.
Figure 5: Inhibition of IL-12-mediated STAT-4 activation by SOCS-3.
Figure 6: Decreased TH2 differentiation in SOCS-3 heterozygous deleted mice and dominant-negative SOCS-3 transgenic mice.

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Acknowledgements

This work was supported by a Grant in Aid for Scientific Research on Priority Areas of the Ministry of Education, Culture, Sports, Science and Technology (Japan). Y.S. is a research fellow of the Japan Society for the Promotion of Science.

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Author notes

  1. Yoh-ichi Seki and Hiromasa Inoue: These authors contributed equally to this work.

Authors and Affiliations

  1. Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, 278-0022, Chiba, Japan

    Yoh-ichi Seki, Katsuhiko Hayashi, Okiru Komine & Masato Kubo

  2. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan

    Hiromasa Inoue, Satoru Fukuyama & Koichiro Matsumoto

  3. Genox Research Inc., 907 Nogawa, Miyamae-ku, 219-0001, Kawasaki, Japan

    Naoko Nagata & Tadahilo Oshida

  4. Department of Parasitology, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan

    Shinjiro Hamano & Kunisuke Himeno

  5. Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Umaide, Higashi-hu, 812-8582, Fukuoka, Japan

    Kyoko Inagaki-Ohara & Akihiko Yoshimura

  6. Department of Radiation Oncology, UCLA Center for Health Sciences, 10833 Le Conte Avenue, Los Angeles, 90095-1714, California, USA

    Nicholas Cacalano

  7. Laboratory of Immunoregulation, The National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Anne O'Garra

  8. RIKEN Research Center for Allergy & Immunology at the National Research Institute for Child Health & Development, 3-35-31, Taishido, Setagaya-ku, 154-8567, Tokyo, Japan

    Hirohisa Saito

  9. Department of Immunology, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland

    James A Johnston

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  1. Yoh-ichi Seki
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Correspondence to Masato Kubo.

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Seki, Yi., Inoue, H., Nagata, N. et al. SOCS-3 regulates onset and maintenance of TH2-mediated allergic responses. Nat Med 9, 1047–1054 (2003). https://doi.org/10.1038/nm896

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