The interleukin-23/interleukin-17 axis in spondyloarthritis.
OBJECTIVE
To inform readers of recent advances in our understanding of the development and function of Th17 T cells and emerging data suggesting that the interleukin-23/interleukin-17 axis may be involved in the pathogenesis of spondyloarthritis.


RESULTS
The discovery of CD4+ Th17 T cells and the interleukin-23/interleukin-17 axis has challenged existing paradigms and the role of Th1 T cells in many autoimmune diseases. The development and cytokine profile of Th17 T cells differs in mice and humans. In humans, interleukin-23 synergizes with interleukin-6 and interleukin-1 to promote Th17 development. In mice, transforming growth factor-beta and interleukin-6 are critical, whereas interleukin-23 is more important at later stages promoting interleukin-17 production. In mice, CD4+ cells producing interferon-gamma appear to be distinct from interleukin-17-producing cells, while in humans cells secreting both cytokines have been observed. Growing evidence from animal models, cytokine analyses of patient fluids, and whole-genome association studies suggest that the interleukin-23/interleukin-17 axis plays an important role in spondyloarthritis pathogenesis. Possible links between an HLA-B27-induced unfolded protein response and activation of the interleukin-23/interleukin-17 axis have been observed in animal models and may contribute to the development of the spondyloarthritis phenotype.


CONCLUSIONS
Activation of the interleukin-23/interleukin-17 axis in spondyloarthritis has important therapeutic implications.
Layh-Schmitt
Gerlinde
G
William S. Rowe Division of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Cincinnati, Ohio, USA.
Colbert
Robert A
RA
D015496:CD4-Positive T-Lymphocytes; D016207:Cytokines; D015796:HLA-B27 Antigen; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D053759:Interleukin-23 / Q000235:genetics*; D011110:Polymorphism, Genetic; D018123:Receptors, Interleukin / Q000235:genetics; D025242:Spondylarthropathies / Q000235:genetics* / Q000276:immunology*
D016207:Cytokines; D015796:HLA-B27 Antigen; C515500:IL23R protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D018123:Receptors, Interleukin