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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Cytokines / genetics
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Cytokines / metabolism
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Cytokines / physiology*
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Humans
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Inflammation Mediators / metabolism
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Inflammation Mediators / physiology*
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Neutrophils / enzymology
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Neutrophils / immunology*
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Neutrophils / metabolism
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Neutrophils / pathology*
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Receptors, Cytokine / genetics
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Receptors, Cytokine / metabolism
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Receptors, Cytokine / physiology
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STAT Transcription Factors / genetics
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STAT Transcription Factors / metabolism
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STAT Transcription Factors / physiology
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Suppressor of Cytokine Signaling Proteins / genetics
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Suppressor of Cytokine Signaling Proteins / metabolism
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Suppressor of Cytokine Signaling Proteins / physiology
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T-Lymphocytes / enzymology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology*
Substances
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Cytokines
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Inflammation Mediators
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Receptors, Cytokine
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STAT Transcription Factors
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Suppressor of Cytokine Signaling Proteins