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Explore how immune dysregulation drives inflammation in PsA

The role of different immune cells in PsA

A dysregulated immune system has many moving parts that act to create the chronic inflammation indicative of disease pathology in SpA. Several types of adaptive and innate immune cells play key roles in mediating inflammation.1

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  • Innate
  • Adaptive

SpA=spondyloarthritis; APCs=antigen presenting cells; DCs=dendritic cells; TNF=tumor necrosis factor; GM-CSF=granulocyte-macrophage colony-stimulating factor; MHC=major histocompatibility complex; TCR=T cell receptor; HLA=human leukocyte antigen; IFN=interferon; Treg=T regulatory cells; AS=ankylosing spondylitis.

Cytokine dysregulation in PsA

Following an injury in the entheses, local cells produce chemo-attractants as mediators of inflammation. This causes local immune cells and innate lymphocytes to secrete cytokines. They enter the circulation and recruit T cells and innate immune cells into the inflamed tissue and produce pro-inflammatory and regulatory cytokines in the enthesial site. In a balanced state, this results in regulated and effective repair mechanisms. However, in PsA, this process is not balanced, and cytokine dysregulation occurs.1,9-11

Cytokine dysregulation is characterized by an excess of inflammatory and/or a depletion of regulatory cytokines, which can lead to pathogenic bone formation. The cytokine balance is influenced by genetic factors, the microbiome, as well as environmental factors, many of which are still unknown.9,10

Cytokine dysregulation in PsA

Genetic risk factors

Studies of HLA alleles and heritability have suggested a stronger genetic component to PsA than psoriasis.1 For example, there are positive associations between HLA-B27 and enthesitis, dactylitis, and symmetric sacroiliitis, and HLA-B08 and HLA-C07 have been linked with joint fusion, asymmetrical sacroiliitis, and dactylitis.1

Influence of the microbiome

Changes are observed in the intestinal microbiome in patients with PsA. The presence of certain gut flora has shown to be correlated with alterations in inflammatory cytokines such as higher levels of secretory IgA and lower concentrations of RANKL.12

HLA=human leukocyte antigen; IgA=immunoglobulin A; RANKL=receptor activator of nuclear factor kappa-B ligand.

Learn more about key cytokines that could be dysregulated, leading to inflammation

Gaze upon the Gallery of Cytokines


Bone damage

Delve into the complex pathogenic processes that can lead to bone damage in patients with PsA

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Overview and role of cytokines

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  2. Kambayashi T, Laufer TM. Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell?. Nat Rev Immunol. 2014;14(11):719-730. doi:10.1038/nri3754
  3. Rezaiemanesh A, Abdolmaleki M, Abdolmohammadi K, et al. Immune cells involved in the pathogenesis of ankylosing spondylitis. Biomed Pharmacother. 2018;100:198-204. doi:10.1016/j.biopha.2018.01.108
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  8. Lai NL, Zhang SX, Wang J, et al. The proportion of regulatory T cells in patients with ankylosing spondylitis: a meta-analysis. J Immunol Res. 2019;2019:1058738. Published 2019. doi:10.1155/2019/1058738
  9. Watad A, Rowe H, Russell T, et al. Normal human enthesis harbours conventional CD4+ and CD8+ T cells with regulatory features and inducible IL-17A and TNF expression. Ann Rheum Dis. 2020;79(8):1044-1054. doi:10.1136/annrheumdis-2020-217309
  10. Watad A, Bridgewood C, Russell T, et al. The early phases of ankylosing spondylitis: emerging insights from clinical and basic science. Front Immunol. 2018;9:2668. Published 2018. doi:10.3389/fimmu.2018.02668
  11. McGonagle DG, McInnes IB, Kirkham BW, et al. The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies [published correction appears in Ann Rheum Dis. 2020;79(1):e12]. Ann Rheum Dis. 2019;78(9):1167-1178. doi:10.1136/annrheumdis-2019-215356
  12. Clemente JC, Manasson J, Scher JU. The role of the gut microbiome in systemic inflammatory disease. BMJ. 2018;360:j5145. Published 2018. doi:10.1136/bmj.j5145
  13. Siebert S, Millar NL, McInnes IB. Why did IL-23p19 inhibition fail in AS: a tale of tissues, trials or translation?. Ann Rheum Dis. 2019;78(8):1015-1018. doi:10.1136/annrheumdis-2018-213654