SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses.
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.
Seki
Yoh-ichi
Y
Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan.
Inoue
Hiromasa
H
Nagata
Naoko
N
Hayashi
Katsuhiko
K
Fukuyama
Satoru
S
Matsumoto
Koichiro
K
Komine
Okiru
O
Hamano
Shinjiro
S
Himeno
Kunisuke
K
Inagaki-Ohara
Kyoko
K
Cacalano
Nicholas
N
O'Garra
Anne
A
Oshida
Tadahilo
T
Saito
Hirohisa
H
Johnston
James A
JA
Yoshimura
Akihiko
A
Kubo
Masato
M
D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology; D001985:Bronchial Provocation Tests; D004268:DNA-Binding Proteins / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D050797:STAT4 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D018418:Th2 Cells / Q000276:immunology* / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D011506:Proteins; D012097:Repressor Proteins; C106644:SOCS3 protein, human; C408990:SOCS5 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C491411:Socs3 protein, mouse; C485811:Socs5 protein, mouse; C494091:Stat4 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D018664:Interleukin-12