SOCS-3 regulates onset and maintenance of T(H)2-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

doi:10.1038/nm896

SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses

Nat Med. 2003 Aug;9(8):1047-54. doi: 10.1038/nm896. Epub 2003 Jun 29.

Authors

Yoh-ichi Seki¹, 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

Affiliation

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

PMID: 12847520
DOI: 10.1038/nm896

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 (T(H)2) cells, but its role in T(H)2-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 T(H)2 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 T(H)2 development. These data indicate that SOCS-3 has an important role in regulating the onset and maintenance of T(H)2-mediated allergic immune disease, and suggest that SOCS-3 may be a new therapeutic target for the development of antiallergic drugs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Asthma / immunology*
Bronchial Hyperreactivity / immunology
Bronchial Provocation Tests
DNA-Binding Proteins / metabolism
Dermatitis, Atopic / immunology*
Humans
Hypersensitivity / immunology*
Hypersensitivity / metabolism
Interleukin-12 / metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Proteins / genetics
Proteins / metabolism*
Repressor Proteins*
STAT4 Transcription Factor
Signal Transduction / physiology
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Th2 Cells / immunology*
Th2 Cells / physiology
Trans-Activators / metabolism
Transcription Factors*

Substances

DNA-Binding Proteins
Proteins
Repressor Proteins
SOCS3 protein, human
SOCS5 protein, human
STAT4 Transcription Factor
STAT4 protein, human
Socs3 protein, mouse
Socs5 protein, mouse
Stat4 protein, mouse
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Trans-Activators
Transcription Factors
Interleukin-12