title: Suppressor of cytokine signaling 4 (SOCS4) protects against severe cytokine storm and enhances viral clearance during influenza infection.
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.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria Australia; Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kedzierski
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria Australia; Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Edmond M
authors.initials: EM
authors.lastname: Linossi
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria Australia; Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Tatiana B
authors.initials: TB
authors.lastname: Kolesnik
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: E Bridie
authors.initials: EB
authors.lastname: Day
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Bird
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria Australia; Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Kile
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria Australia; Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria Australia; Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Donald
authors.initials: D
authors.lastname: Metcalf
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria Australia; Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Nicos A
authors.initials: NA
authors.lastname: Nicola
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kedzierska
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria Australia; Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Nicholson
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000009:adverse effects* / Q000378:metabolism*; D019610:Cytoprotection / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000009:adverse effects / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology*; D019562:Viral Load / Q000235:genetics
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C472529:SOCS4 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins