IL-27-induced modulation of autoimmunity and its therapeutic potential

Abstract

Interleukin-27 (IL-27) is a new member of the IL-12 family. It is produced by activated antigen-presenting cells and plays an important role in the regulation of CD4+ T cell differentiation and immune response. IL-27 activates multiple signaling cascades, including the JAK-STAT and p38 MAPK pathways. Several studies have revealed that IL-27 promotes the differentiation of Th1 and Tr1, but inhibits Th2, Th17, and Treg cells. However, a few studies have shown an opposite effect on certain T cell subsets, such as Treg. IL-27 displays both pro- and anti- inflammatory activities in different autoimmune diseases. Here, we have discussed the role of IL-27 in rheumatoid arthritis, multiple sclerosis, colitis, lupus, psoriasis, type 1 diabetes, and uveitis. Most of this information is derived from experimental models of these autoimmune diseases. The mechanistic basis of the dual role of IL-27 in inflammation and autoimmunity is still not fully defined. In general, the pro-/ anti- inflammatory activity of IL-27 is influenced by the underlying immune effector pathways, the phase of the disease, the presence or absence of counter-regulatory cytokines/T cell subsets, and the tissue/cell type under study. Despite a spectrum of outcomes in various autoimmune diseases, mostly anti-inflammatory and immunomodulatory effects of IL-27 have been observed in this category of diseases. Accordingly, IL-27 represents a novel, promising target/agent for the treatment of autoimmune diseases.

IL-27 Is Essential for Suppression of Experimental Allergic Asthma by the TLR7/8 Agonist R848 (Resiquimod)

“…The heterodimeric IL-27 cytokine usually binds its receptor complex composed of IL-27Ra/WSX-1 and gp130 to activate STAT1 and induce Th1 cell differentiation (32)(33)(34)(35)(36). The IL-27Ra/WSX-1 receptor is abundantly expressed on CD4 + T cells, and its binding by IL-27 leads to polarization of naive Th cells toward Th1 and thus inhibition of Th2 cytokine production in activated T cells (60).…”

“…IL-27 is a member of the IL-12 family and primarily produced by activated DCs and pulmonary macrophages (30)(31)(32). This heterodimeric cytokine binds to the IL-27 receptor and gp130 to activate STAT1 (33)(34)(35) and induce Th1 cell differentiation (32,36) whereas it directly suppresses Th2 and Th17 differentiation (37).…”

“…This heterodimeric cytokine binds to the IL-27 receptor and gp130 to activate STAT1 (33)(34)(35) and induce Th1 cell differentiation (32,36) whereas it directly suppresses Th2 and Th17 differentiation (37). Very recently, it was shown in different models of lung inflammation, including allergic inflammation and viral respiratory tract infection, that IFNs and IL-27 regulate the function of group 2 innate lymphoid cells and thereby together restrict type 2 immune responses (38)(39)(40).…”

Induction of regulatory T cells: A role for probiotics and prebiotics to suppress autoimmunity

“…Recently, IL-27 has been shown to exert dual effects on Tregs by activating multiple signaling cascades, including the JAK-STAT and p38 MAPK pathways and suggested as a novel, promising target/agent for the treatment of autoimmune diseases [130]. IL-27…”

Interleukin-27 as a Novel Therapy for Inflammatory Bowel Disease

“…6 Several excellent reviews have recently discussed the biology of IL-27. 6–9 The purpose of this review is to highlight recent literature investigating the role of IL-27 in IBD, and to discuss possible explanations for the conflicting results of these studies. Evidence supporting IL-27 therapy as a potential treatment for IBD will also be discussed.…”