The mechanism by which SOCS3 mediates IL-10 inhibition of macrophage activation

Inflammation is a protective response generated by immune cells against infection. However, when inflammation becomes unregulated within the body, it can cause diseases. A key anti-inflammatory regulator of immune cells is a cytokine (a type of hormone), called interleukin-10 (IL-10). The importance of IL-10 in regulating immune cell function is illustrated by the fact that many tumour cells and intracellular pathogens produce or elicit production of IL-10 for their survival. A main target of IL-10 is macrophages. Activation of macrophages by interferons, or bacterial cell products such as lipopolysaccharide (LPS), induces a number of immunologic responses including production of pro-inflammatory mediators such as the cytokine TNF. IL-10 is able to suppress these events by interfering with pathways utilized by LPS, but its mechanism is unclear. Previous research on the intracellular signal transduction pathways utilized by IL-10 has shown that an important component is a protein called SOCS3 which is thought to target specific proteins for degradation. In order to understand how IL-10 uses SOCS3 to inhibit macrophage activation, Tsz Ying Sylvia Cheung’s research is focusing on proteins that interact with SOCS3 in cells stimulated with IL-10. Identification of these proteins will allow for a further research focus on understanding the role they play in macrophage activation and why they are targeted by IL-10. Developing a clear understanding of the mechanism by which IL-10 regulates the network of intracellular signal transduction pathways will better enable the development of therapeutics mimicking the beneficial anti-inflammatory effects of IL-10, and allow for the development of strategies to counter the immunosuppressive effects of certain tumours and immune cell pathogens.