Tolerogenic XCR1+ dendritic cell population is dysregulated in HLA-B27 transgenic rat model of spondyloarthritis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Arthritis Research & Therapy Année : 2019

Tolerogenic XCR1+ dendritic cell population is dysregulated in HLA-B27 transgenic rat model of spondyloarthritis

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Background: Spondyloarthritis (SpA) is a chronic inflammatory disease affecting primarily axial and peripheral joints and sometimes also extra-articular organs, such as the gut. Rats transgenic for HLA-B27 and human β2-microglobulin (B27-Tg rat) develop clinical manifestations resembling human disease. In this model, it has been shown that CD103+ conventional dendritic cells (cDCs) exhibited altered functions, likely promoting SpA development. CD4− cDC subpopulation expressing XCR1, a chemokine receptor involved in their migration, have been described to be tolerogenic in steady state. Thus, in this study, we wished to examine the fate of XCR1+ cDCs in this animal model of SpA. Methods: cDC populations were isolated from the spleen, mesenteric lymph nodes (MLN), and colonic lamina propria from B27-TG and control nontransgenic (NTG) and/or HLA-B7 transgenic rats after collagenase digestion and density gradient and characterized with flow cytometry or real-time PCR. Migration of cDCs from intestinal mucosa to MLN was assessed, using TLR-7 stimulation with Resiquimod. Results: We observed a reduced frequency of cCD4− DCs in B27-Tg rats, as compared to control rats. Furthermore, such decrease was not due to excessive death of CD4− cDCs in B27-Tg rats. Interestingly, we observed a decrease frequency of the XCR1+ subpopulation among CD4− cDCs in the spleen, MLN, and lamina propria from B27-Tg rats. Finally, after TLR-7 stimulation, the migration of XCR1+ cDCs to MLN was proportionally reduced in B27-Tg rats. Conclusion: Our results demonstrate for the first time a decreased proportion of the tolerogenic XCR1+ cDC subpopulation in SpA target organs in B27-Tg rat, which may affect the maintenance of self-tolerance and control of inflammation
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hal-04547388 , version 1 (15-04-2024)

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Kétia Ermoza, Simon Glatigny, Nadège Jah, Vânia Camilo, Hendrick Mambu Mambueni, et al.. Tolerogenic XCR1+ dendritic cell population is dysregulated in HLA-B27 transgenic rat model of spondyloarthritis. Arthritis Research & Therapy, 2019, 21 (1), pp.46. ⟨10.1186/s13075-019-1827-9⟩. ⟨hal-04547388⟩
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