1. Tolerogenic XCR1 + dendritic cell population is dysregulated in HLA-B27 transgenic rat model of spondyloarthritis.
- Author
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Ermoza K, Glatigny S, Jah N, Camilo V, Mambu Mambueni H, Araujo LM, Chiocchia G, and Breban M
- Subjects
- Animals, Antigens, CD immunology, Cell Movement genetics, Cell Movement immunology, Cells, Cultured, Dendritic Cells metabolism, Disease Models, Animal, HLA-B27 Antigen genetics, HLA-B27 Antigen metabolism, Humans, Immune Tolerance genetics, Immune Tolerance immunology, Inflammation genetics, Inflammation immunology, Inflammation metabolism, Integrin alpha Chains immunology, Rats, Inbred F344, Rats, Transgenic, Receptors, Chemokine genetics, Receptors, Chemokine metabolism, Spondylarthritis genetics, Spondylarthritis metabolism, beta 2-Microglobulin genetics, beta 2-Microglobulin metabolism, Dendritic Cells immunology, HLA-B27 Antigen immunology, Receptors, Chemokine immunology, Spondylarthritis immunology, beta 2-Microglobulin immunology
- Abstract
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.- Published
- 2019
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