Pathobiology

Overview

Spondyloarthritis pathobiology is complex

There are many clinically validated targets involved in spondyloarthritis pathobiology, including IL-17, TNF, IL-12, IL-23 and JAK/STAT. Here, we focus on extracellular cytokine targets IL-17, TNF, IL-12 and IL-23.¹

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Watch Prof Sewerin decipher the role of extracellular cytokine targets in SpA pathobiology by playing the animation below

There are many clinically validated targets involved in spondyloarthritis pathobiology, including IL-17, TNF, IL-12, IL-23 and JAK/STAT. Although the relative contributions of each are complex, important distinctions are emerging about which cytokines contribute to the various clinical manifestations and SpA disease phenotypes.2,3,9,10,11 Emerging studies are revealing a new dimension of complexity in the IL-17 pathway that may help explain its in vivo functions.12

What is the role of the different cytokines in the IL-17 family?

Whilst different in structure, IL-17A and IL-17F have a very similar biological function.13 IL-17A and IL-17F combine to form homo- and heterodimers.14

Role of the different cytokines in the IL-17 family
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References
1
McGonagle DG et al. Front Immunol. 2021;12:614255.
2
McGonagle DG et al. Ann Rheum Dis. 2019;78(9):1167–1178.
3
Rosine N, Miceli-Richard C. Front Immunol. 2021;11:553742.
4
Tsukazaki H, Kaito T. Int J Mol Sci. 2020;21(17):6401.
5
Cole S et al. Front Immunol. 2020;11:585134.
6
Blanco P et al. Cytokine Growth Factor Rev. 2008;19(1):41–52.
7
Russell T et al. Cells. 2021;10(2):341.
8
Glatt S et al. Ann Rheum Dis. 2018;77:523–532.
9
Rezaiemanesh A et al. Biomed Pharmacother. 2018;100:198–204.
10
Hammitzsch A et al. Front Immunol. 2020;11:591176.
11
Siebert S et al. Ann Rheum Dis. 2019;78(8):1015–1018.
12
Li X et al. Nat Immunol. 2019;20(12):1594–1602.
13
Yang XO et al. J Exp Med. 2008;205(5):1063–1075.
14
Goepfert A et al. Immunity. 2020;52(3):499–512.
15
Toy D et al. J Immunol. 2006;177(1):36–39.
16
Wright JF et al. J Immunol. 2008;181(4):2799–2805​.
17
Rickel EA et al. J Immunol. 2008;181:4299–4310.
18
Chang SH et al. Immunity. 2011;35(4):611–621.
19
Shi Y et al. J Biol Chem. 2000;275(25):19167–19176.
20
Starnes T et al. J Immunol. 2002;169(2):642–646.
21
Yang RB et al. J Biol Chem. 2003;278(35):33232–33238.
22
Monin L et al. Cold Spring Harb Perspect Biol. 2018;10(4)a028522.
23
Jadon DR et al. Nat Rev Rheumatol. 2020;16(11):609–627.
24
Shah M et al. RMD Open. 2020;6(2):e001306.
25
Fossiez F et al. J Exp Med. 1996;183:2593–2603.
26
Hymowitz SG et al. EMBO J. 2001;20(19):5332–5341.
27
Fort MM et al. Immunity. 2001;15:985–995.
28
Puel A et al. Curr Opin Immunol. 2010;22(4):467–474.
29
Ishigame H et al. Immunity. 2009;30(1):108–119.
30
Owyang AM et al. J Exp Med. 2006;203(4):843–849.
Acronyms
APC
antigen-presenting cell
axSpA
axial spondyloarthritis
CCL
C-C motif chemokine ligand
CNS
central nervous system
G-CSF
granulocyte colony-stimulating factor
IL
interleukin
ILC
innate lymphoid cell
JAK
Janus kinase
MAIT
mucosal-associated invariant T cell
PsA
psoriatic arthritis
STAT
signal transducer and activator of transcription
Th
T helper cell
TNF
tumour necrosis factor