Aberrant expression of suppressor of cytokine signaling (SOCS) molecules contributes to the development of allergic diseases

Abstract

AbstractSuppressor of cytokine signalling (SOCS) proteins bind to certain cytokine receptors, Janus kinases and signalling molecules to regulate signalling pathways, thus controlling immune and inflammatory responses. Dysregulated expression of various types of SOCS molecules was indicated in multiple types of allergic diseases. SOCS1, SOCS2, SOCS3, SOCS5, and cytokine‐inducible SH2 domain protein (CISH) can differentially exert anti‐allergic impacts through different mechanisms, such as suppressing Th2 cell development and activation, reducing eosinophilia, decreasing IgE production, repressing production of pro‐allergic chemokines, promoting Treg cell differentiation and activation, suppressing Th17 cell differentiation and activation, increasing anti‐allergic Th1 responses, inhibiting M2 macrophage polarization, modulating survival and development of mast cells, reducing pro‐allergic activity of keratinocytes, and suppressing pulmonary fibrosis. Although some anti‐allergic effects were attributed to SOCS3, it can perform pro‐allergic impacts through several pathways, such as promoting Th2 cell development and activation, supporting eosinophilia, boosting pro‐allergic activity of eosinophils, increasing IgE production, enhancing the expression of the pro‐allergic chemokine receptor, reducing Treg cell differentiation, increasing pro‐allergic Th9 responses, as well as supporting mucus secretion and collagen deposition. In this review, we discuss the contrasting roles of SOCS proteins in contexts of allergic disorders to provide new insights regarding the pathophysiology of these diseases and possibly explore SOCS proteins as potential therapeutic targets for alleviating allergies.