Cross-regulation of Signaling and Immune Responses by IFN-γ and STAT1

By Xiaoyu Hu, L. Ivashkiv. Immunity, 2009

907 citations recorded by the source corpus.

Summary IFN-γ is an important mediator of immunity and inflammation that utilizes the Jak-STAT pathway to activate STAT1. Many functions of IFN-γ have been ascribed to direct STAT1-mediated induction of immune effector genes, but recently it has become clear that key IFN-γ functions are mediated by crossregulation of cellular responses to other cytokines and inflammatory factors. Here we review mechanisms by which IFN-γ and STAT1 regulate signaling by TLRs, inflammatory factors, tissue destructive cytokines, anti-inflammatory cytokines, and cytokines that activate opposing STATs. These signaling mechanisms reveal insights about how IFN-γ regulates macrophage activation, inflammation, tissue remodeling, and Th and Treg differentiation, and how Th1 and Th17 responses are integrated in autoimmune diseases.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/11d62dc27d8383bbb5fe0a3dad5369c1b8b357fd

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In Immunology

1. S. Gordon
2. F. Martínez
3. A. Mantovani
4. A. Sica
5. Tamás Rőszer
6. TA Wynn
7. P. Murray
8. T. Lawrence

In Oncology

1. F. Martínez
2. S. Gordon

Citations in the corpus

• Astrocytes: Key Regulators of Neuroinflammation. (2016, background): “During CNS inflammation IFN-g acts in multifaceted ways, as it may initiate oligodendrocyte death [25] and contribute to macrophage and microglia activation [26] or support neuroprotection by negative regulation of neutrophil and T cell accumulation [27–29].”
• The M1 and M2 paradigm of macrophage activation: time for reassessment (2014, background): “The receptor recruits Janus kinase (Jak)1 and Jak2 adaptors that activate STAT1 (signal transducers and activators of transcription1) and interferon regulatory factors (IRF), such as IRF-1 and IRF-8; for a recent comprehensive review, see [13].”
• Innate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression (2014, background): “Interindividual variation in the early (2 hours) and late (24 hours) inflammatory responses to lipopolysaccharide (LPS), a component of gramnegative bacterial cell walls that triggers TLR4 signaling (10), and interferon-g (IFN-g) (24 hours), a cytokine acting through the JAK-STAT (Janus kinase–signa”
• Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses (2010, neutral): “Lack of a detectable increase in Th2 and Th17 responses in the presence of miR-146a-deficient Treg cells can be explained by the fact that IFNg/Stat1 signaling, while promoting Th1 immune response, inhibits the differentiation of Th2 and Th17 cells (Hu and Ivashkiv, 2009).”