New insights into IL‑17/IL‑23 signaling in ankylosing spondylitis (Review)

Abstract

Ankylosing spondylitis (AS) is a progressive common autoimmune inflammatory disease, part of the spondylarthritis group, characterized, besides clinical spinal and peripheral joint inflammation, by enthesitis and new bone formation, that can lead to severe functional impairment. Beyond intensive and continuous research on the pathogenic process extensively performed in recent years, their impact on therapeutic management remains open to future development. Better knowledge of AS pathogenesis have shown results progressively and studies are being performed to advance our current understanding of the disease. It is well known that tumor necrosis factor (TNF) exerts a central role, along with interleukin-17 (IL-17) and interleukin-23 (IL-23), demonstrated by several clinical studies. Similar to other rheumatic inflammatory conditions, SA is associated with an early process of systemic bone loss, both trabecular and cortical, consecutive osteopenia, osteoporosis, and high fracture risk. Current personalized therapeutic options benefit from new published data, to prevent future complications and to improve quality of life. Contents 1. Introduction 2. Immunopathogenesis of ankylosing spondylitis 3. Effects of IL-23 and IL-17 on the bone 4. Conclusions

Effect of Warming Yang, Tonifying Kidney, and Removing Arthralgia Therapy on Cold-Dampness Arthralgia Type Ankylosing Spondylitis and Its Influence on the Levels of Humoral Factor in Human Serum

“…Dickkopf-1 protein (DKK-1) not only exists in the flat bone but also is expressed in tubular bone cells, and its level is negatively correlated with bone mineral density [ 4 ]. Interleukin-17 (IL-17) is the main factor secreted by Th17 cells [ 5 ]. TNF- α is a common inflammatory factor, directly involved in the occurrence and development of AS.…”

Effects of Biological/Targeted Therapies on Bone Mineral Density in Inflammatory Arthritis

“…Surprisingly, the unique bone phenotype that occurs in PsA and AS coexists with both systemic bone destruction and new bone formation, which is likely to be the result of the actions of IL-23 and/or IL-17 on osteocytes [101,102]. IL-17, the prevailing inflammatory cytokine in many SpA patients, has been found to promote not only osteoclasts for bone resorption but also osteoblasts for bone formation [103,104]. IL-23 is another distinctive cytokine that is abundantly present in the affected skin or joints of PsA patients [103].…”

IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation

“…Examples of inflammatory diseases accompanied with extensive systemic and local bone degradation include rheumatoid arthritis 3 , 4 and psoriatic arthritis (PsA) 5 . In contrast, ankylosing spondylitis is associated with early process of systemic bone loss, but demonstrates extensive bone formation in the spine and periphery at later stages 6 .…”

“…Notably, in both extremes, a role for Interleukin-23 (IL-23) has been reported 6 – 8 . IL-23 belongs to the IL-12 cytokine family, and is composed of a heterodimer of the subunits IL-23p19 and IL-12p40 9 , 10 .…”