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
Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan.
Nat Med. 2003 Aug;9(8):1047-54. doi: 10.1038/nm896. Epub 2003 Jun 29.
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.
细胞因子信号转导抑制因子(SOCS)家族成员参与多种炎症性疾病的发病机制。SOCS-3主要在2型辅助性T细胞(T(H)2)中表达,但其在与T(H)2相关的过敏性疾病中的作用仍有待研究。在本研究中,我们发现SOCS-3表达与哮喘和特应性皮炎的病理以及过敏性人类患者的血清IgE水平之间存在密切关联。在气道超敏反应模型系统中,SOCS-3转基因小鼠表现出增强的T(H)2反应和哮喘的多种病理特征。相比之下,显性负性突变SOCS-3转基因小鼠以及Socs3杂合缺失的小鼠,其T(H)2发育减少。这些数据表明,SOCS-3在调节T(H)2介导的过敏性免疫疾病的发生和维持中起重要作用,并提示SOCS-3可能是开发抗过敏药物的新治疗靶点。