Abstract
The IL-1 family consists of 11 cytokines, 7 ligands with agonist activity (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ) and four members with antagonistic activities [IL-1 receptor antagonist (IL-1Ra), IL-36Ra, IL-37, IL-38]. Recent articles have described that most members of IL-1 family cytokines are involved in the process of innate and adaptive immunity as well as fibrosis in systemic sclerosis (SSc). IL-1 family gene polymorphisms, abnormal expression of IL-1 and its potential role in the fibrosis process have been explored in SSc. IL-33 and IL-18 have also been discussed in the recent years. IL-33 may contribute to the fibrosis of SSc, while IL-18 remains to be researched to confirm its role in fibrosis process. There is a lack of study on the pathophysiological roles of IL-36, IL-37, and IL-38 in SSc, which might provide us new study area. Here, we aim to give a brief overview of IL-1 family cytokines and discuss their pivotal roles in the pathogenesis of SSc.
Highlights
Systemic sclerosis (SSc) is an idiopathic autoimmune disease characterized by immune dysfunction, vasculopathy, and progressive fibrosis in skin and internal organs
IL-1 family cytokines activate signal transduction by the IL-1 receptor (IL-1R) family, which consists of 10 members: IL-1R1, IL-1R2, IL-1R accessory protein (IL-1RAcP), IL-18Rα, IL-18Rβ, ST2, IL-36R, single Ig IL-1R-related molecule (SIGIRR), three Ig domain-containing IL-1R related2 (TIGGIR-2), and TIGGIR-1 [9]
Pro-inflammatory cytokines of IL-1 family (IL-1α, IL-1β, IL18, IL-33, IL-36) bind to similar conserved receptors consisting of extracellular Ig domains and intracellular TIR domains and induce cell activation through recruiting cytoplasmic myeloid differentiation primary response protein 88 (MyD88), IL-1R associated kinase 4 (IRAK4), tumor necrosis factor receptorassociated factor 6 (TRAF6), which ends up in the activation of nuclear factor-κB (NF-κB), and mitogen-activated protein kinase (MAPK) [10]
Summary
Systemic sclerosis (SSc) is an idiopathic autoimmune disease characterized by immune dysfunction, vasculopathy, and progressive fibrosis in skin and internal organs. The etiology and pathogenesis of immune abnormalities and fibrosis in SSc are poorly understood, which leads to a lack of effective treatments for SSc. The current treatment is mainly non-specific symptomatic treatment, which can only temporarily improve the condition but cannot fundamentally control the progress of fibrosis [2]. Recent findings show that expression of most IL-1 family cytokines, such as IL-1α, IL-1β, IL-18, and IL-33, was abnormal in many autoimmune diseases including SSc. gene polymorphisms of IL-1α, IL-1β, IL-18, and IL-33 were reported to be correlated with SSc susceptibility. IL-18Rα ( termed IL-18R1 or IL-1R5) ST2 ( termed IL-1R4) IL-36R ( termed IL-1R6) IL-36R IL-18Rα
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