Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Apr 24;23(5):31.
doi: 10.1007/s11926-021-00995-y.

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

Akihiro Nakamura  1   2   3   4   5 , Nigil Haroon  6   7   8   9   10
Affiliations
Review

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

Akihiro Nakamura et al. Curr Rheumatol Rep. .

Abstract

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 γδ 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.

Keywords: Enthesitis; GM-CSF; IL-22; IL23/IL-17 axis; Spondyloarthritis.

PubMed Disclaimer

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
    1. Schett G, Lories RJ, D’Agostino M-A, Elewaut D, Kirkham B, Soriano ER, et al. Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol. 2017;13:731–41. - PubMed
    1. Vaquero-Picado A, Barco R, Antuña SA. Lateral epicondylitis of the elbow. EFORT Open Rev. 2016;1:391–7. - PubMed - PMC
    1. Benjamin M, Moriggl B, Brenner E, Emery P, McGonagle D, Redman S. The “enthesis organ” concept: why enthesopathies may not present as focal insertional disorders. Arthritis Rheum. 2004;50:3306–13.
    1. Watad A, Rowe H, Russell T, et al (2020) Normal human enthesis harbours conventional CD4+ and CD8+ T cells with regulatory features and inducible IL-17A and TNF expression. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2020-217309 . This study shows that conventional CD4+ and CD8+ T cells exist in human anxial entheses and have an ability to produce IL-17A and TNF.
    1. Cuthbert RJ, Watad A, Fragkakis EM, et al. Evidence that tissue resident human enthesis γδT-cells can produce IL-17A independently of IL-23R transcript expression. Ann Rheum Dis. 2019;78:1559 LP–1565 This study provides the first evidence of IL-17 producing γδ T cells independent of IL-23 in human axial entheses, which may be the reason for the ineffectiveness of IL-23 monoclonal antibodies in patients with ankylosing spondylitis.

Publication types

Grants and funding

LinkOut - more resources