Rheumatology
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Understanding the Complexity of SpA Pathobiology

There are many clinically validated targets that drive pathogenic inflammation in spondyloarthritis, including IL-17, TNF, IL-12*, IL-23* and JAK-STAT.1–3

What are the cytokines implicated in SpA pathobiology?​

IL-17A and IL-17F are pivotal drivers of inflammation in PsA, axSpA, PSO and HS.4–7 They share overlapping biology,8–14 and can be produced by multiple lymphocyte subsets, a process which can be independent of IL-23.2,15,16

IL-17A and IL-17F:

Form homodimers and heterodimers9,10

Use the same receptor complex11,12

Are both expressed at sites of inflammation in PsA, axSpA, PSO, and HS4,7,13,14,17,18

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Figure adapted from references8–14

However, IL-17A and IL-17F are also regulated and expressed differently:​

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Regulation

 

STAT5 induces preferential expression of IL-17F over IL-17A, whereas STAT3 enhances ​IL-17A over IL-17F20

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Kinetics

 

Over time IL-17F becomes the dominant cytokine expressed by Th17 cells20†

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Target Tissue Expression

 

IL-17F expression is high relative to IL-17A in tissues and in vitro models of PsA ​and axSpA20–22

†IL-17A is more potent than IL-17F in human skin cells, whilst IL-17F is more abundant than IL-17A in patients with psoriasis.21 CD4+ T cells stimulated with anti-CD3 and anti-CD28 in addition to brefeldin A between 0–72 hours.20​

What disease manifestations are these cytokines implicated in? ​

 

Explore our resources below to find out the answers to this question and more today.​

*Validated for PsA but failed for axSpA.1 

Abbreviations

axSpA: axial spondyloarthritis; CD: cluster of differentiation; HS: hidradenitis suppurativa; IL: interleukin; JAK: Janus kinase; PsA: psoriatic arthritis; PSO: psoriasis; SpA: spondyloarthritis; STAT: signal transducer and activator of transcription; Th: T helper cell; TNF: tumour necrosis factor.

References

  1. McGonagle DG et al. Front Immunol. 2021;12:614255. ​
  2. Tsukazaki H, Kaito T. Int J Mol Sci. 2020;21(17):6401. ​
  3. McInnes IB et al. Rheumatology (Oxford). 2022;61(5):1783–1794. ​
  4. Glatt S et al. Ann Rheum Dis. 2018;77(4):523–532.​
  5. Glatt S et al. JAMA Dermatol. 2021;157(11):1279–1288. ​
  6. Shah M et al. RMD Open. 2020;6(2):e001306. ​
  7. Navarro-Compán V et al. Front Immunol. 2023;14:1191782.​
  8. Hymowitz SG et al. EMBO J. 2001;20(19):5332–5341. ​
  9. Chang SH, Dong C. Cell Res. 2007;17(5):435–440. ​
  10. Wright JF et al. J Biol Chem. 2007;282(18):13447–13455.​
  11. McAllister F et al. J Immunol. 2005;175(1):404–412. ​
  12. Kuestner RE et al. J Immunol. 2007;179(8):5462–5473. ​
  13. Yang XO et al. J Exp Med. 2008;205(5):1063–1075. ​
  14. van Baarsen LGM et al. Arthritis Res Ther. 2014;16(4):426. ​
  15. Cole S et al. Front Immunol. 2020;11:585134.​
  16. Łukasik Z et al. Rheumatology (Oxford). 2021;60(Suppl 4):iv16–27. ​
  17. Wright JF et al. J Immunol. 2008;181(4):2799–2805. ​
  18. Sánchez-Rodríguez G Puig L. Int J Mol Sci. 2023;24(12):10305. ​
  19. Maroof A, Maghera A, Shaw S. SID 2022. P010. ​
  20. Cole S et al. J Allergy Clin Immunol. 2023;152(3):783–798. ​
  21. Kolbinger F et al. J Allergy Clin Immunol. 2017;139(3):923–932. ​
  22. McDermott N et al. Ann Rheum Dis. 2023;82:1184. AB0011. 

EU-DC-2400159

 

Date of preparation: February 2025