Cytokine Signaling Modules in Inflammatory Responses

• Published in: Immunity (Cambridge, Mass.) Vol. 28; no. 4; pp. 477 - 487
• Main Authors: O'Shea, John J., Murray, Peter J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2008; Elsevier Limited
• Subjects: Animals; Autoimmune diseases; Cytokines; Cytokines - genetics; Cytokines - metabolism; Cytokines - physiology; Humans; Immune system; Inflammation Mediators - metabolism; Inflammation Mediators - physiology; Kinases; Mutation; Neutrophils - enzymology; Neutrophils - immunology; Neutrophils - metabolism; Neutrophils - pathology; Receptors, Cytokine - genetics; Receptors, Cytokine - metabolism; Receptors, Cytokine - physiology; Rodents; Signal Transduction - genetics; Signal Transduction - immunology; STAT Transcription Factors - genetics; STAT Transcription Factors - metabolism; STAT Transcription Factors - physiology; 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
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2008.03.002

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.