Cytokine signaling modules in inflammatory responses.
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.
O'Shea
John J
JJ
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20852, USA. osheajo@mail.nih.gov
Murray
Peter J
PJ
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
D016207:Cytokines; D018836:Inflammation Mediators; D018121:Receptors, Cytokine; D050791:STAT Transcription Factors; D050826:Suppressor of Cytokine Signaling Proteins