Suppressors of Cytokine Signaling 2 and 3 Diametrically Control Macrophage Polarization

Shaun Spence, Amy Fitzsimons, Caroline R. Boyd, Julia Kessler, Denise Fitzgerald, Joanne Elliott, Joan Ní Gabhann, Siobhan Smith, Antonio Sica, Emily Hams, Sean P. Saunders, Caroline A. Jefferies, Padraic G. Fallon, Danny F. McAuley, Adrien Kissenpfennig, James A. Johnston

Research output: Contribution to journalArticlepeer-review

Abstract

Suppressors of cytokine signaling (SOCS) are important regulators of lipopolysaccharide (LPS) and cytokine responses but their role in macrophage polarization is unknown. We have shown here that myeloid-restricted Socs3 deletion (Socs3Lyz2cre) resulted in resistance to LPS-induced endotoxic shock, whereas Socs2-/- mice were highly susceptible. We observed striking bias toward M2-like macrophages in Socs3Lyz2cre mice, whereas the M1-like population was enriched in Socs2-/- mice. Adoptive transfer experiments showed that responses to endotoxic shock and polymicrobial sepsis were transferable and macrophage dependent. Critically, this dichotomous response was associated with enhanced regulatory T (Treg) cell recruitment by Socs3Lyz2cre cells, whereas Treg cell recruitment was absent in the presence of Socs2-/- macrophages. In addition, altered polarization coincided with enhanced interferon-gamma (IFN-γ)-induced signal transducer and activator of transcription-1 (STAT1) activation in Socs2-/- macrophages and enhanced interleukin-4 (IL-4) plus IL-13-induced STAT6 phosphorylation in Socs3Lyz2cre macrophages. SOCS, therefore, are essential controllers of macrophage polarization, regulating inflammatory responses.

Original languageEnglish
Pages (from-to)66-78
Number of pages13
JournalImmunity
Volume38
Issue number1
DOIs
Publication statusPublished - Jan 24 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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