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

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-019-1827-9) contains supplementary material, which is available to authorized users.