The suppressors of cytokine signalling (SOCS) proteins are negative regulators of cytokine signalling, immune cell development and function, and the inflammatory response. SOCS1-3 and CIS have defined roles in controlling the magnitude of response to various cytokines including the interferons, gp130 cytokines, IL-12, IL-10, G-CSF, prolactin, growth hormone and IL-2 family cytokines. We have recently shown SOCS4 to be a critical regulator of the anti-viral response, with loss of functional SOCS4 leading to increased susceptibility to influenza infection (1). Given the similarity between the SOCS4 and 5 SH2 domains, and the lack of an obvious phenotype in mice lacking SOCS5 protein (Socs5-/-), we have investigated its role during influenza infection. Socs5-/- mice were also highly susceptible to infection with H1N1 Puerto Rico/8/34 (PR8) influenza A virus, displaying an increased morbidity and mortality, which is associated with increased weight loss, elevated proinflammatory cytokines and delayed viral clearance. In contrast to Socs4-deficient mice, these differences are evident at day 2 post-infection, suggesting that the innate immune response is perturbed. In addition, Socs5 mRNA is expressed at significantly higher levels than Socs4 in lung epithelium, the primary site of viral replication, and is upregulated in response to infection. An intrinsic defect in epithelial cells was confirmed by infection of cultured primary lung epithelial cells from Socs5-/- mice. Moreover, wild-type bone marrow transfer into irradiated Socs5-/- mice did not rescue the phenotype, confirming the non-hematopoietic nature of the defect. We are currently using proteomics and siRNA knock-down studies to identify the innate signalling pathways that are regulated by SOCS5.

(1) Kedzierski et al., PLOS Pathogens 2014, 10(5):e1004134