Suppressor of Cytokine Signaling 4 (SOCS4) Protects against Severe Cytokine Storm and Enhances Viral Clearance during Influenza Infection |
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| Authors: | Lukasz Kedzierski Edmond M Linossi Tatiana B Kolesnik E Bridie Day Nicola L Bird Benjamin T Kile Gabrielle T Belz Donald Metcalf Nicos A Nicola Katherine Kedzierska Sandra E Nicholson |
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| Institution: | 1. Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria Australia.; 2. Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.; 3. Department of Microbiology and Immunology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.; National Institutes of Health, United States of America, |
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| Abstract: | 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. |
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