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

  • Spondyloarthritis (M Khan, Section Editor)
  • Published:
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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.

Summary

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.

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Funding

This article was supported by grants to NH from the Canadian Institute of Health Research (CIHR) and Arthritis Society. AN is a recipient of CIHR fellowship, Spondyloarthritis Research and Treatment Network (SPARTAN) fellowship, Spondyloarthritis Research Consortium of Canda (SPARCC) fellowship, and Krembil fellowship award.

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Authors and Affiliations

  1. Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada

    Akihiro Nakamura & Nigil Haroon

  2. Spondylitis Program, University Health Network, Toronto, Ontario, Canada

    Akihiro Nakamura & Nigil Haroon

  3. Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada

    Akihiro Nakamura & Nigil Haroon

  4. Division of Rheumatology, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada

    Akihiro Nakamura & Nigil Haroon

  5. Institute of Medical Science, Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    Akihiro Nakamura & Nigil Haroon

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  1. Akihiro Nakamura
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Correspondence to Nigil Haroon.

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Nakamura, A., Haroon, N. Recent Updates in the Immunopathology of Type 3 Immunity-Mediated Enthesitis. Curr Rheumatol Rep 23, 31 (2021). https://doi.org/10.1007/s11926-021-00995-y

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