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

Abstract

Suppressor 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.

The Interplay Between Helicobacter pylori and Suppressors of Cytokine Signaling (SOCS) Molecules in the Development of Gastric Cancer and Induction of Immune Response

“…Numerous cytokines and chemokines, such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), transforming growth factor-β (TGF-β), interleukin-1 (IL-1), IL-2, IL-6, IL-10, IL-17, IL-23, C-X-C motif chemokine ligand 12 (CXCL12), and CXCL4 are released both at the site of infection and in the systemic circulation [8][9][10][11]. The JAK/STAT pathway is the major signal transduction mechanism for a large number of cytokines [12].…”

“…Activation of immune cells, especially different subsets of the effector CD4 + T cells may be significant in determining the clinical consequence of H. pylori infection [8,10]. It was also clearly approved that some SOCS molecules affect the T-cell differentiation [12]. However, the direct effects of SOCS molecules on the differentiation of different T-cell subsets during H. pylori infection remains to be clarified in future studies.…”

“…It has been established that some SOCS molecules influence the development of diverse subgroups of effector T cells [12]. SOCS1 inhibits the development of Th1 cells, but is required for Th17 cell differentiation [123][124][125][126].…”

“…Suppressors of cytokine signaling (SOCS) proteins are essential for controlling cytokine-induced signaling pathways by acting as negative feedback controllers of cytokine signaling (Figure 1) [12,14]. These proteins block cytokine-induced signaling in a variety of ways, including competitively interacting with STAT molecules at certain phosphorylated regions of the cytokine receptor, guiding target proteins toward proteasomal degradation, and blocking kinase activity [15].…”

“…The eight members of the SOCS family (SOCS1-7, and cytokine-inducible SH2 domain protein [CIS]) have a similar structural organization specified by a C-terminal SOCS box and a central Src homology 2 (SH2) domain (Figure 1) [16]. Dysregulated expression of SOCS proteins has been associated with the susceptibility to some infections, various types of immune-related diseases (autoimmune and allergic diseases) as well as different types of cancers, including breast cancer, hepatocellular carcinoma (HCC), prostate cancer, colorectal cancer, leukemia, and glioblastoma [12,14,17,18]. Abnormal expression of SOCS has been also observed in immune cells within tumors, suggesting their roles in regulating antitumor immune responses [19].…”