Suppressor of Cytokine Signaling 4 (SOCS4) Protects against Severe Cytokine Storm and Enhances Viral Clearance during Influenza Infection e1004134
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 pa...
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Published in | PLoS pathogens Vol. 10; no. 5 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
San Francisco
Public Library of Science
01.05.2014
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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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AbstractList | 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. |
Author | Day, E Bridie Metcalf, Donald Linossi, Edmond M Belz, Gabrielle T Kedzierski, Lukasz Nicholson, Sandra E Bird, Nicola L Kile, Benjamin T Kedzierska, Katherine Nicola, Nicos A Kolesnik, Tatiana B |
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ContentType | Journal Article |
Copyright | 2014 Kedzierski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Kedzierski L, Linossi EM, Kolesnik TB, Day EB, Bird NL, et al. (2014) Suppressor of Cytokine Signaling 4 (SOCS4) Protects against Severe Cytokine Storm and Enhances Viral Clearance during Influenza Infection. PLoS Pathog 10(5): e1004134. doi:10.1371/journal.ppat.1004134 |
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DOI | 10.1371/journal.ppat.1004134 |
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SubjectTerms | Bone marrow Chemokines Cytokines Flow cytometry Immune system Infections Kinases Lungs Lymphocytes Mortality Proteins Scholarships & fellowships Swine flu T cell receptors Viral infections |
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Title | Suppressor of Cytokine Signaling 4 (SOCS4) Protects against Severe Cytokine Storm and Enhances Viral Clearance during Influenza Infection |
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