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Review
. 2021 Feb 22:12:637829.
doi: 10.3389/fimmu.2021.637829. eCollection 2021.

Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview

Claudia Schinocca  1 , Chiara Rizzo  1 , Serena Fasano  2 , Giulia Grasso  1 , Lidia La Barbera  1 , Francesco Ciccia  2 , Giuliana Guggino  1
Affiliations
Review

Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview

Claudia Schinocca et al. Front Immunol. .

Abstract

Interleukin-23 (IL-23) is a pro-inflammatory cytokine composed of two subunits, IL-23A (p19) and IL-12/23B (p40), the latter shared with Interleukin-12 (IL-12). IL-23 is mainly produced by macrophages and dendritic cells, in response to exogenous or endogenous signals, and drives the differentiation and activation of T helper 17 (Th17) cells with subsequent production of IL-17A, IL-17F, IL-6, IL-22, and tumor necrosis factor α (TNF-α). Although IL-23 plays a pivotal role in the protective immune response to bacterial and fungal infections, its dysregulation has been shown to exacerbate chronic immune-mediated inflammation. Well-established experimental data support the concept that IL-23/IL-17 axis activation contributes to the development of several inflammatory diseases, such as PsA, Psoriasis, Psoriatic Arthritis; AS, Ankylosing Spondylitis; IBD, Inflammatory Bowel Disease; RA, Rheumatoid Arthritis; SS, Sjogren Syndrome; MS, Multiple Sclerosis. As a result, emerging clinical studies have focused on the blockade of this pathogenic axis as a promising therapeutic target in several autoimmune disorders; nevertheless, a greater understanding of its contribution still requires further investigation. This review aims to elucidate the most recent studies and literature data on the pathogenetic role of IL-23 and Th17 cells in inflammatory rheumatic diseases.

Keywords: IL-17; IL-23; IL-23/IL-17 axis; autoimmune diseases; inflammatory diseases.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic image of the cascade of cytokines and transcription factors involved in the differentiation of Th1 and Th17 cells. IFN-γ, interferon-γ; IL, interleukin; RORγt, retinoid-related orphan receptor γt, STAT, signal transducer and activator of transcription; GATA, GATA transcription factor; TGF-β, transforming growth factor β, Th, T helper.
Figure 2
Figure 2
Pathogenesis of IL-17-correlated disease and different targets of therapy. IFN-γ, interferon-γ; IL, interleukin; Th, T helper; TNF-α, Tumor necrosis factor.
See this image and copyright information in PMC

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