Figure 3.

Schematic diagram of the proposed role of genetic and environmental factors in the pathogenesis of AS. As shown in the figure, auto-reactive CD8⁺ T cells may recognize arthritogenic peptides displayed by HLA-B27 on the anti-gene presenting cell surface and cause misfolding of HLA-B27 which leads to stress in the ER and consequently causes overproduction of IL-23. On the other hand, abnormal cell-surface expression of HLA-B27 leads to interactions with the innate immune receptor KIR3DL2 (killer immunoglobulin-like receptor) on CD4⁺T cells and promotes type 17 immune responses. Environmental factors (like microbes present in gut) activate HLA-B27, which cause intestinal dysbiosis, resulting in overexpression of the IL-17A. IL-23 axis with the activation of Th17 and other innate immune cells. This leads to the production of IL-17A, IL-22, TNF-α, TNF-γ and other cytokines which directly affect organs.

Abbreviations: ER, endoplasmic reticulum; AS, ankylosing spondylitis; HLA, human leukocyte antigen; TNF, tumor necrosis factor.