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Tolerogenic XCR1 + dendritic cell population is dysregulated in HLA-B27 transgenic rat model of spondyloarthritis.
- Source :
-
Arthritis research & therapy [Arthritis Res Ther] 2019 Feb 04; Vol. 21 (1), pp. 46. Date of Electronic Publication: 2019 Feb 04. - Publication Year :
- 2019
-
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 <superscript>+</superscript> conventional dendritic cells (cDCs) exhibited altered functions, likely promoting SpA development. CD4 <superscript>-</superscript> 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 <superscript>+</superscript> cDCs in this animal model of SpA.<br />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.<br />Results: We observed a reduced frequency of cCD4 <superscript>-</superscript> DCs in B27-Tg rats, as compared to control rats. Furthermore, such decrease was not due to excessive death of CD4 <superscript>-</superscript> cDCs in B27-Tg rats. Interestingly, we observed a decrease frequency of the XCR1 <superscript>+</superscript> subpopulation among CD4 <superscript>-</superscript> cDCs in the spleen, MLN, and lamina propria from B27-Tg rats. Finally, after TLR-7 stimulation, the migration of XCR1 <superscript>+</superscript> cDCs to MLN was proportionally reduced in B27-Tg rats.<br />Conclusion: Our results demonstrate for the first time a decreased proportion of the tolerogenic XCR1 <superscript>+</superscript> cDC subpopulation in SpA target organs in B27-Tg rat, which may affect the maintenance of self-tolerance and control of inflammation.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1478-6362
- Volume :
- 21
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Arthritis research & therapy
- Publication Type :
- Academic Journal
- Accession number :
- 30717755
- Full Text :
- https://doi.org/10.1186/s13075-019-1827-9