Serum amyloid A overrides Treg anergy via monocyte-dependent and Treg-intrinsic, SOCS3-associated pathways

Blood. 2011 Apr 7;117(14):3793-8. doi: 10.1182/blood-2010-11-318832. Epub 2011 Feb 16.

Abstract

The acute phase protein serum amyloid A (SAA) has been well characterized as an indicator of inflammation. Nevertheless, its functions in pro versus anti-inflammatory processes remain obscure. Here we provide unexpected evidences that SAA induces the proliferation of the tolerogenic subset of regulatory T cells (T(reg)). Intriguingly, SAA reverses T(reg) anergy via its interaction with monocytes to activate distinct mitogenic pathways in T(reg) but not effector T cells. This selective responsiveness of T(reg) correlates with their diminished expression of SOCS3 and is antagonized by T(reg)-specific induction of this regulator of cytokine signaling. Collectively, these evidences suggest a novel anti-inflammatory role of SAA in the induction of a micro-environment that supports T(reg) expansion at sites of infection or tissue injury, likely to curb (auto)-inflammatory responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Child
  • Clonal Anergy / drug effects*
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / physiology*
  • Serum Amyloid A Protein / pharmacology*
  • Serum Amyloid A Protein / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / antagonists & inhibitors*
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Suppressor of Cytokine Signaling Proteins / physiology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / physiology

Substances

  • Serum Amyloid A Protein
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins