Suppressor of cytokine signaling 4 (SOCS4) protects against severe cytokine storm and enhances viral clearance during influenza infection

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

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article numbere1004134
Number of pages13
JournalPLoS Pathogens
Volume10
Issue number5
DOIs
Publication statusPublished - 8 May 2014
Externally publishedYes

Keywords

  • T cells
  • cytotoxic T cells
  • cytokines
  • influenza
  • respiratory infections
  • spleen
  • chemokines
  • infectious disease control

Cite this

Kedzierski, Lukasz ; Linossi, Edmond M. ; Kolesnik, Tatiana B. ; Day, E. Bridie ; Bird, Nicola L ; Kile, Benjamin T. ; Belz, Gabrielle T. ; Metcalf, Donald ; Nicola, Nicos A. ; Kedzierska, Katherine ; Nicholson, Sandra E. / Suppressor of cytokine signaling 4 (SOCS4) protects against severe cytokine storm and enhances viral clearance during influenza infection. In: PLoS Pathogens. 2014 ; Vol. 10, No. 5.
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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.",
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author = "Lukasz Kedzierski and Linossi, {Edmond M.} and Kolesnik, {Tatiana B.} and Day, {E. Bridie} and Bird, {Nicola L} and Kile, {Benjamin T.} and Belz, {Gabrielle T.} and Donald Metcalf and Nicola, {Nicos A.} and Katherine Kedzierska and Nicholson, {Sandra E.}",
year = "2014",
month = "5",
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Kedzierski, L, Linossi, EM, Kolesnik, TB, Day, EB, Bird, NL, Kile, BT, Belz, GT, Metcalf, D, Nicola, NA, Kedzierska, K & Nicholson, SE 2014, 'Suppressor of cytokine signaling 4 (SOCS4) protects against severe cytokine storm and enhances viral clearance during influenza infection' PLoS Pathogens, vol. 10, no. 5, e1004134. https://doi.org/10.1371/journal.ppat.1004134

Suppressor of cytokine signaling 4 (SOCS4) protects against severe cytokine storm and enhances viral clearance during influenza infection. / Kedzierski, Lukasz; Linossi, Edmond M.; Kolesnik, Tatiana B.; Day, E. Bridie; Bird, Nicola L; Kile, Benjamin T.; Belz, Gabrielle T.; Metcalf, Donald; Nicola, Nicos A.; Kedzierska, Katherine; Nicholson, Sandra E.

In: PLoS Pathogens, Vol. 10, No. 5, e1004134, 08.05.2014.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Kedzierski, Lukasz

AU - Linossi, Edmond M.

AU - Kolesnik, Tatiana B.

AU - Day, E. Bridie

AU - Bird, Nicola L

AU - Kile, Benjamin T.

AU - Belz, Gabrielle T.

AU - Metcalf, Donald

AU - Nicola, Nicos A.

AU - Kedzierska, Katherine

AU - Nicholson, Sandra E.

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AB - 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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