Suppressor of Cytokine Signaling 4 (SOCS4) Protects against Severe Cytokine Storm and Enhances Viral Clearance during Influenza Infection

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The suppressor of cytokine signaling proteins are key regulators of immunity. As yet there is no described biological role for SOCS4, despite its broad expression in cells of the immune system. Given the important role of other SOCS proteins in controlling the immune response, we have generated SOCS4-mutant mice and used a mouse influenza infection model to investigate the biological function of SOCS4. We demonstrate that mice lacking SOCS4 rapidly succumb to infection with a pathogenic H1N1 influenza virus and are hypersusceptible to infection with the less virulent H3N2 strain. This is the first demonstration of a functional phenotype in SOCS4-deficient mice. Our study reveals that in SOCS4-deficient animals, there is a dysregulated pro-inflammatory cytokine and chemokine production in the lungs and delayed viral clearance. This is associated with impaired trafficking of virus-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. Understanding the regulation of the inflammatory response to influenza is particularly relevant given the current climate concerning pandemic influenza outbreaks.

Vyšlo v časopise: Suppressor of Cytokine Signaling 4 (SOCS4) Protects against Severe Cytokine Storm and Enhances Viral Clearance during Influenza Infection. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004134
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004134

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