Dendritic Cells of Mesenteric and Regional Lymph Nodes Contribute to Yersinia enterocolitica O:3–Induced Reactive Arthritis in TNFRp55 −/− Mice

SILVA, JUAN E.; MAYORDOMO, ANDREA C.; DAVE, MABEL N.; AGUILERA MERLO, CLAUDIA; ELIÇABE, RICARDO J.; DI GENARO, MARÍA S.

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Año: 2020 vol. 204 p. 1859 - 1868

0022-1767

Dendritic cells (DCs) participate in the pathogenesis of several diseases. We investigated DCs and the connection between mucosa and joints in a murine model of Yersinia enterocolitica O:3?induced reactive arthritis (ReA) in TNFRp552/2 mice. DCs of mesenteric lymph nodes (MLN) and joint regional lymph nodes (RLN) were analyzed in TNFRp552/2 and wild-type mice. On day 14 after Y. enterocolitica infection (arthritis onset), we found that under TNFRp55 deficiency, migratory (MHChighCD11c+) DCs increased significantly in RLN. Within these RLN, resident (MHCintCD11c+) DCs increased on days 14 and 21. Similarchanges in both migratory and resident DCs were also detected on day 14 in MLN of TNFRp552/2 mice. In vitro, LPS-stimulated migratory TNFRp552/2 DCs of MLN increased IL-12/23p40 compared with wild-type mice. In addition, TNFRp552/2 bonemarrow?derived DCs in a TNFRp552/2 MLN microenvironment exhibited higher expression of CCR7 after Y. enterocolitica infection. The major intestinal DC subsets (CD103+CD11b2, CD1032CD11b+, and CD103+CD11b+) were found in the RLN of Y. enterocolitica?infected TNFRp552/2 mice. Fingolimod (FTY720) treatment of Y. enterocolitica?infected mice reduced the CD11b2 subset of migratory DCs in RLN of TNFRp552/2 mice and significantly suppressed the severity of ReA in these mice. This result was associated with decreased articular IL-12/23p40 and IFN-g levels. In vitro FTY720 treatment downregulated CCR7 on Y. enterocolitica?infected bone marrow?derived DCs and purified MLN DCs, which may explain the mechanism underlying the impairment of DCs in RLN induced by FTY720. Taken together, data indicate the migration of intestinal DCs to RLN and the contribution of these cells in the immunopathogenesis of ReA, which may provide evidence for controlling this disease.