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Published on: February 19, 2019
SOCS3, a Major Regulator of Infection and Inflammation
Berit Carow1, Martin E Rottenberg1
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm , Sweden.
Abstract:
In this review, we describe the role of suppressor of cytokine signaling-3 (SOCS3) in modulating the outcome of infections and autoimmune diseases as well as the underlying mechanisms. SOCS3 regulates cytokine or hormone signaling usually preventing, but in some cases aggravating, a variety of diseases. A main role of SOCS3 results from its binding to both the JAK kinase and the cytokine receptor, which results in the inhibition of STAT3 activation. Available data also indicate that SOCS3 can regulate signaling via other STATs than STAT3 and also controls cellular pathways unrelated to STAT activation. SOCS3 might either act directly by hampering JAK activation or by mediating the ubiquitination and subsequent proteasome degradation of the cytokine/growth factor/hormone receptor. Inflammation and infection stimulate SOCS3 expression in different myeloid and lymphoid cell populations as well as in diverse non-hematopoietic cells. The accumulated data suggest a relevant program coordinated by SOCS3 in different cell populations, devoted to the control of immune homeostasis in physiological and pathological conditions such as infection and autoimmunity.
Insights
Suppressor of cytokine signaling-3 (SOCS3) is a key regulator of immune responses, influencing infections and autoimmune diseases by controlling cytokine signaling pathways. Understanding SOCS3 mechanisms is crucial for immune homeostasis.
Area of Science:
- Immunology
- Molecular Biology
- Cellular Signaling
Background:
- Suppressor of cytokine signaling-3 (SOCS3) plays a critical role in immune regulation.
- SOCS3 modulates cytokine and hormone signaling pathways.
- Dysregulation of SOCS3 is implicated in various diseases.
Purpose of the Study:
- To review the role of SOCS3 in infections and autoimmune diseases.
- To elucidate the underlying molecular mechanisms of SOCS3 action.
- To highlight SOCS3's function in immune homeostasis.
Main Methods:
- Literature review of studies on SOCS3 function.
- Analysis of SOCS3's interactions with JAK kinases and cytokine receptors.
- Examination of SOCS3's regulation of STAT3 and other signaling pathways.
- Investigation of SOCS3 expression in various cell types.
Main Results:
- SOCS3 inhibits STAT3 activation by binding to JAK kinases and cytokine receptors.
- SOCS3 can regulate signaling pathways beyond STAT3.
- SOCS3 mediates receptor degradation via ubiquitination.
- Inflammation and infection induce SOCS3 expression in diverse cell populations.
Conclusions:
- SOCS3 is a central coordinator of immune homeostasis.
- SOCS3's dual role in preventing or aggravating diseases depends on context.
- Targeting SOCS3 pathways offers potential therapeutic strategies for immune-related disorders.
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