Cytokine Signaling Modules in Inflammatory Responses

Immunity. 2008 Apr;28(4):477-87. doi: 10.1016/j.immuni.2008.03.002.

Abstract

Cytokine signaling via a restricted number of Jak-Stat pathways positively and negatively regulates all cell types involved in the initiation, propagation, and resolution of inflammation. Here, we focus on Jak-Stat signaling in three major cell types involved in inflammatory responses: T cells, neutrophils, and macrophages. We summarize how the Jak-Stat pathways in these cells are negatively regulated by the Suppressor of cytokine signaling (Socs) proteins. We emphasize that common Jak-Stat-Socs signaling modules can have diverse developmental, pro- and anti-inflammatory outcomes depending on the cytokine receptor activated and which genes are accessible at a given time in a cell's life. Because multiple components of Jak-Stat-Socs pathways are mutated or closely associated with human inflammatory diseases, and cytokine-based therapies are increasingly deployed to treat inflammation, understanding cytokine signaling will continue to advance our ability to manipulate chronic and acute inflammatory diseases.

Publication types

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

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Cytokines / physiology*
  • Humans
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology*
  • Neutrophils / enzymology
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Neutrophils / pathology*
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism
  • Receptors, Cytokine / physiology
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • STAT Transcription Factors / physiology
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Suppressor of Cytokine Signaling Proteins / physiology
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology*

Substances

  • Cytokines
  • Inflammation Mediators
  • Receptors, Cytokine
  • STAT Transcription Factors
  • Suppressor of Cytokine Signaling Proteins