Prostaglandin E2 and IL-23 interconnects STAT3 and RoRγ pathways to initiate Th17 CD4+ T-cell development during rheumatoid arthritis.

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The chronic inflammation associated with rheumatoid arthritis (RA) leads to focal and systemic bone erosion of the joints resulting in a crippling disability. Recent reports indicate an increase in the incidence of RA in the coming years, placing a significant burden on healthcare resources. The incidence of RA is observed to be increasing with age and a significant proportion of those new cases will be aggressively erosive. The altered physiology, due to immune disturbances, contributes towards RA pathogenesis. The imbalance of inflammatory cytokines and non-cytokine immune modulators such as prostaglandin E2 (PGE2) and IL-23-induced pathogenic IL-17, plays a crucial role in persistent inflammation and bone degradation during RA. However, the molecular mechanism of IL-23, a key cytokine, and PGE2 in the development and perpetuation of IL-17 producing effector Th17 cells is poorly understood. This review focuses on research findings that provide insight into the contribution of PGE2 and IL-23 during the development of pathogenic Th17 cells. We also highlight the key transcriptional factors required for Th17 development and therapeutic strategies to disrupt the interaction between IL-23 and IL-17 to prevent the end-organ damage in RA.