IL-23/IL-17 Axis in Inflammatory Rheumatic Diseases
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IL‑23/IL‑17 Axis in Inflammatory Rheumatic Diseases Hao Li1 · George C. Tsokos1 Accepted: 2 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract In inflammatory rheumatic disorders, the immune system attacks and damages the connective tissues and invariably internal organs. During the past decade, remarkable advances having been made towards our understanding on the cellular and molecular mechanisms involved in rheumatic diseases. The discovery of IL-23/IL-17 axis and the delineation of its important role in the inflammation led to the introduction of many needed new therapeutic tools. We will present an overview of the rationale for targeting therapeutically the IL-23/IL-17 axis in rheumatic diseases and the clinical benefit which has been realized so far. Finally, we will discuss the complex interrelationship between IL-23 and IL-17 and the possible uncoupling in certain disease settings. Keywords Inflammatory rheumatic disorders · IL-23/IL-17 axis · Biologics
Introduction Inflammatory rheumatic disorders are a group of diseases with variable phenotypic presentation [1–5]. However, the presence of either systemic inflammation or organ-specific inflammation is a common feature of these diseases [6, 7]. During the past decade, the identification of the proinflammatory function of interleukin-17 (IL-17) [8–10] and the discovery of a novel subset of T helper cells termed Th17 cells [11, 12] which drive inflammation by producing IL-17, the signature cytokine, have led to important insights into chronic inflammation. Interleukin-23 (IL-23), a heterodimeric cytokine comprising two subunits (p19 and p40), controls the production of pro-inflammatory cytokines including IL-17, IL-22, and GM-CSF by promoting the development and expansion of pathogenic Th17 cells [13]. This relationship between IL-23 and Th17s has led to the concept of the IL-23–IL-17 axis as a pivotal pathway driving various autoimmune processes [13-15] Rheumatic diseases are the most common cause of disability and over 50 million Americans are living with some * Hao Li [email protected] George C. Tsokos [email protected] 1
Departments of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
form of rheumatic diseases [16–18].Until late twentieth century, the main drugs available for the treatment of rheumatic diseases were limited to the use of classical disease-modifying antirheumatic drugs (DMARDs) which were developed without full understanding of involved cellular or molecular mechanisms [19, 20]. The introduction of biologic therapeutics at the end of the twentieth century has contributed significantly to the improvement in the management of these diseases [21]. However, considering the fact that no matter which novel biologics, there are always a significant proportion of patients who fail to respond; the effort to further understand the involved mechanisms and the identification of new targets should not abate. Genetic and experimental data support the c
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