The role of gut microbiota and IL-23/IL-17 pathway in ankylosing spondylitis immunopathogenesis: New insights and updates

Abstract

Ankylosing spondylitis (AS) is a type of arthritis that is referred to a group of chronic immune-mediated inflammatory diseases termed as seronegative spondyloarthropathies or spondyloarthritides. It typically affects the joints of the spinal and axial skeleton and exhibits common clinical features and genetic factors such as human leukocyte antigen class I allele HLA-B27, the Endoplasmic Reticulum Aminopeptidase 1 (ERAP1), and environmental factors such as microbial triggers. Although the precise etiopathogenic mechanisms that implicate the pathogenesis of AS have still remained to be clarified, the IL-23/IL-17 immune axis has been detected as an important factor in the immunopathogenesis of AS. Moreover, therapeutic options targeting this signaling pathway have been demonstrated to be effective in various other inflammatory diseases that share similar genetic etiology and pathogenetic pathways. In mammalian intestinal, there are trillions of commensal microbes that create the intricate symbiotic relationship with host well-known as the microbiota and play the major role in human health and disease. Several publications have appeared in recent years documenting the pivotal role of the gut microbiota and the IL-23/IL-17 pathway in the pathogenesis of spondyloarthritides. In this review, several points are discussed and summarized including recent advances on the role of the IL-17/IL-23 immune pathway in the pathogenesis of AS, HLA-B27, and ERAP 1 and 2 mediated pathogenesis, AS-related microbiota compositions, and new potential therapies for AS.

Keywords: Ankylosing spondylitis; Dysbiosis; ERAP1; IL-17; IL-23; Microbiome; Therapy.