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Article
Nature Medicine  9, 1047 - 1054 (2003)
Published online: 29 June 2003; | doi:10.1038/nm896

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

Yoh-ichi Seki1, 10, Hiromasa Inoue2, 10, Naoko Nagata3, Katsuhiko Hayashi1, Satoru Fukuyama2, Koichiro Matsumoto2, Okiru Komine1, Shinjiro Hamano4, Kunisuke Himeno4, Kyoko Inagaki-Ohara5, Nicholas Cacalano6, Anne O'Garra7, Tadahilo Oshida3, Hirohisa Saito8, James A Johnston9, Akihiko Yoshimura5 & Masato Kubo1

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

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

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

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

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

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

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

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

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

10  These authors contributed equally to this work.

Correspondence should be addressed to Masato Kubo raysolfc@rs.noda.tus.ac.jp
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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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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