Recent Updates in the Immunopathology of Type 3 Immunity-Mediated Enthesitis

Purpose of Review Enthesitis is a cardinal feature of spondyloarthritis (SpA). Despite increasing available treatments, challenges remain in adequately controlling inflammation and subsequent new bone formation (NBF) in entheses; thus, a better understanding of the immunopathogenesis is warranted. Recent Findings Increasing evidence has identified immune cells playing key roles in enthesitis such as gamma delta T cells and group 3 innate lymphoid cells (ILC3), possibly with site-specific regulatory systems. The presence of T cells producing interleukin (IL)-17 independent of IL-23 in human spinal entheses was recently reported, which may corroborate the discrepancy between recent clinical trials and pre-clinical studies. In addition, the contribution of myeloid cells has also been focused in both human and pre-clinical SpA models. Moreover, not only the IL-23/IL-17 signaling, but other key type 3 immunity mediators, such as IL-22 and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been reported as pivotal cytokines in inflammation and NBF of entheses. Immune cells demonstrating distinct features orchestrate entheses, leading to the complex landscape of enthesitis. However, recent advances in understanding the immunopathogenesis may provide new therapeutic targets and future research directions.

Automated summary

Enthesitis is a key feature of spondyloarthritis, where immune cells play crucial roles in inflammation and new bone formation. Research has identified not only the IL-23/IL-17 signaling, but also other key cytokines in this process, providing new therapeutic targets and research directions.