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Article Abstract
Objective: Spondyloarthritis (SpA) is a group of chronic inflammatory disorders associated with the human leukocyte antigen (HLA) class I allele HLA-B27. Transgenic rats expressing HLA-B27 and human β2-microglobulin (B27 rats) develop clinical manifestations resembling SpA called rat SpA. IL-17 and TNF are key proinflammatory cytokines implicated in both human and rat SpA. We aimed to determine which T cell subset(s) produce IL-17 and TNF during rat SpA, characterize their tissue distribution and tested their pathogenicity in vivo.
Methods: Cytokine production by T cell subsets was evaluated in target tissues and lymphoid organs during rat SpA. Pathogenicity of purified IL-17 cells was assessed in vivo by cell transfer. Blood samples were used to translate B27 rats findings to SpA patients.
Results: Conventional CD4 T cells (Foxp3; Tconv) and γδ T cells were the main producers of both IL-17 and TNF in B27 rats. IL-17-producing Tconv and γδ T cells were expanded in the colon of premorbid 3-weeks-old B27 rats. C-C motif chemokine receptor 6 (CCR6) allowed the isolation of IL-17 Tconv (Th17) in rat. Transfer of B27 rat IL-17-producing CCR6 Tconv but not of γδ T cells into disease-free nude B27 rats induced arthritis, directly demonstrating for the first time the arthritogenic potential of Th17 cells in SpA. Finally, a CCR6 IL-17 Tconv expansion enriched for IL-17F production was evidenced in SpA patients.
Conclusion: Our study demonstrates that IL-17TNFCCR6 Th17 cells and IL-17 γδ T cells are expanded preceding SpA onset in B27 rats and that only IL-17TNFCCR6 Th17 cells can trigger arthritis.
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| http://dx.doi.org/10.1016/j.jaut.2025.103413 | DOI Listing |
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