Kedzierski Lukasz, Linossi Edmond M, Kolesnik Tatiana B, Day E Bridie, Bird Nicola L, Kile Benjamin T, Belz Gabrielle T, Metcalf Donald, Nicola Nicos A, Kedzierska Katherine, Nicholson Sandra E
Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria Australia; Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
PLoS Pathog. 2014 May 8;10(5):e1004134. doi: 10.1371/journal.ppat.1004134. eCollection 2014 May.
Suppressor of cytokine signaling (SOCS) proteins are key regulators of innate and adaptive immunity. There is no described biological role for SOCS4, despite broad expression in the hematopoietic system. We demonstrate that mice lacking functional SOCS4 protein rapidly succumb to infection with a pathogenic H1N1 influenza virus (PR8) and are hypersusceptible to infection with the less virulent H3N2 (X31) strain. In SOCS4-deficient animals, this led to substantially greater weight loss, dysregulated pro-inflammatory cytokine and chemokine production in the lungs and delayed viral clearance. This was associated with impaired trafficking of influenza-specific CD8 T cells to the site of infection and linked to defects in T cell receptor activation. These results demonstrate that SOCS4 is a critical regulator of anti-viral immunity.
细胞因子信号转导抑制因子（SOCS）蛋白是先天性和适应性免疫的关键调节因子。尽管SOCS4在造血系统中广泛表达，但尚未发现其有明确的生物学作用。我们证明，缺乏功能性SOCS4蛋白的小鼠会迅速死于致病性H1N1流感病毒（PR8）感染，并且对毒性较弱的H3N2（X31）毒株感染高度敏感。在缺乏SOCS4的动物中，这导致体重显著减轻、肺部促炎细胞因子和趋化因子产生失调以及病毒清除延迟。这与流感特异性CD8 T细胞向感染部位的迁移受损有关，并与T细胞受体激活缺陷有关。这些结果表明，SOCS4是抗病毒免疫的关键调节因子。
