Aberrant IL-4 production by SOCS3-over-expressing T cells during infection with Leishmania major exacerbates disease manifestations.
Aberrant IL-4 production by SOCS3-over-expressing T cells during infection with Leishmania major exacerbates disease manifestations.
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DOI：
10.1093/intimm/dxq472
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发表时间：
2011-03
影响因子：
4.4
通讯作者：
M. Nakaya;S. Hamano;M. Kawasumi;H. Yoshida;A. Yoshimura;Takashi Kobayashi
中科院分区：
文献类型：
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作者：
M. Nakaya;S. Hamano;M. Kawasumi;H. Yoshida;A. Yoshimura;Takashi Kobayashi
细胞因子信号转导抑制因子3（SOCS）是信号转导和转录激活因子3激活细胞因子的主要负反馈调节因子。使用T细胞特异性SOCS 3缺陷型小鼠的研究表明，由于T（h）3细胞表型的偏斜，伴随着IL-10和转化生长因子β（TGF-β）的过度产生，T细胞中SOCS 3的缺失导致感染硕大利什曼原虫后疾病进展的加剧。在这里，我们表明，在T细胞中过表达SOCS 3基因的转基因小鼠（Lck-SOCS 3 Tg小鼠）也容易受到L.少校T细胞中SOCS 3的强制表达不会影响抗炎细胞因子IL-10和TGF-β的产生，也不会影响清除寄生虫所需的保护性T（h）1型细胞因子IFN-γ的产生。从感染Lck-SOCS 3 Tg小鼠分离的CD 4（+）T细胞在用L.体外主要抗原。Lck-SOCS 3 Tg小鼠中疾病进展的加重通过施用针对IL-4的中和抗体而完全逆转。这些数据表明，T（h）细胞中SOCS 3表达的严格调节对于L.少校
Suppressor of cytokine signaling (SOCS) 3 is a major negative feedback regulator of signal transducer and activator of transcription 3-activating cytokines. Studies using T-cell-specific SOCS3-deficient mice indicate that the absence of SOCS3 in T cells results in exacerbation of disease progression after infection by Leishmania major due to skewing of the T(h)3 cell phenotype accompanied by hyper-production of IL-10 and transforming growth factor β (TGF-β). Here we show that transgenic mice over-expressing the SOCS3 gene in T cells (Lck-SOCS3 Tg mice) are also susceptible to infection by L. major. Forced expression of SOCS3 in T cells did not affect the production of the anti-inflammatory cytokines IL-10 and TGF-β or that of the protective T(h)1 type cytokine IFN-γ, which is required for parasite clearance. CD4(+) T cells isolated from infected-Lck-SOCS3 Tg mice produced much higher levels of IL-4 when they were re-stimulated with L. major antigen in vitro. Exacerbation of disease progression in Lck-SOCS3 Tg mice was completely reversed by administration of a neutralizing antibody against IL-4. These data suggest that tight regulation of SOCS3 expression in T(h) cells is crucial for disease control during infection by L. major.