Suppressor of cytokine signaling (SOCS) proteins are mainly induced by various cytokines and have been described as classical inhibitors of cytokine signaling. SOCS signaling is involved in the regulation of immune cells, and recent findings suggest that SOCS proteins, especially SOCS1 and SOCS3, are often dysregulated in a wide variety of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, psoriasis, and multiple sclerosis. Recent studies suggest that SOCS signaling could be therapeutically targeted in various autoimmune diseases. In this review, we discuss recent studies on the role of SOCS proteins in the development and pathogenesis of autoimmune diseases, as well as their clinical implications.Keywords: Autoimmune disease r Signaling pathways r Suppressor of cytokine signaling IntroductionCytokines are secreted glycoproteins that regulate diverse physiologic and pathologic responses through their interaction with multisubunit receptor complexes. Receptors of the cytokine superfamily transmit their signaling via intracellular kinases pathways, such as JAK-STAT signaling pathways. Dysregulation of cytokine signaling pathways has been correlated with development and pathogenesis of many autoimmune diseases. Several years ago, the regulators of cytokine pathways called suppressors of cytokine signaling (SOCS) were described [1]. It has been recognized that the expression levels of SOCS are low in the basal state, but are rapidly induced by the JAK-STAT pathway [2]. The upregulated SOCS protein expression in turn triggers a negative feedback process for overactivated cytokine signaling via several inhibitory mechanisms [2]. In this review, we summarize our current underCorrespondence: Prof. Dong-Qing Ye e-mail: ydqahmu@gmail.com standing of the involvement of SOCS proteins in the development and pathogenesis of autoimmune diseases, as well as their clinical implications and novel therapeutic strategies. SOCS protein familyThe SOCS family consists of eight proteins, SOCS1-SOCS7 and CIS, each of which has a central SH2 domain, an amino-terminal domain of varying length and sequence and a carboxy-terminal 40-amino-acid-long module known as the SOCS box [2] (Fig. 1). Cytokine receptor signaling has been found to rapidly induce SOCS protein expression. SOCS proteins are swiftly degraded when cytokine signaling ceases and usually remain inactive in resting cells. Thus, SOCS signaling might have a central role in many immunological processes including immune cell development, differentiation, and function. Although all SOCS proteins share the same basic structure, some intriguing differences among them have been recently recognized. SOCS1 and SOCS3 lack any introns and have an additional domain in their amino-terminal region, which has been named kinase inhibitory region (KIR) [3]. Moreover, SOCS4-SOCS7 exhibit an extended C-terminus [3]. Notably, there are some pairs of SOCS family (CIS and SOCS2; SOCS1 and SOCS3; SOCS4 and SOCS5; and SOCS6 and SOCS7) that display mar...

Interleukin (IL)-36 is a member of the IL-1 superfamily and includes three agonists (IL-36α, IL-36β, and IL-36γ) and an antagonist (IL-36Ra). IL-36 agonists bind to heterodimeric receptor complexes. Then, the heterotrimer complexes signal via intracellular functional domains, binding to downstream signaling proteins and inducing inflammatory responses. In this review, we summarized the current knowledge about the biological role of IL-36 and its correlation with systemic inflammatory diseases. The information collected will help to increase the understanding of the potential of IL-36 and may give clues for developing novel therapeutic strategies.

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MicroRNAs (miRNAs) are a group of approximately 20-22-nucleotide-long non-coding RNAs that repress target gene expression through mRNA degradation and translation inhibition. MiRNA (miR)-146a, located in the second exon of the LOC285628 gene on human chromosome 5, is a negative regulator in immune and inflammatory responses. Studies have indicated that miR-146a is associated with the pathogenesis of several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome. In this review, emphasis will be laid on the recent progress in the functional roles of miR-146a in these autoimmune diseases.