PMID- 32122996 OWN - NLM STAT- MEDLINE DCOM- 20201023 LR - 20211204 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 204 IP - 7 DP - 2020 Apr 1 TI - Dendritic Cells of Mesenteric and Regional Lymph Nodes Contribute to Yersinia enterocolitica O:3-Induced Reactive Arthritis in TNFRp55(-/-) Mice. PG - 1859-1868 LID - 10.4049/jimmunol.1901137 [doi] AB - 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 TNFRp55(-/-) mice. DCs of mesenteric lymph nodes (MLN) and joint regional lymph nodes (RLN) were analyzed in TNFRp55(-/-) and wild-type mice. On day 14 after Y. enterocolitica infection (arthritis onset), we found that under TNFRp55 deficiency, migratory (MHC(high)CD11c(+)) DCs increased significantly in RLN. Within these RLN, resident (MHC(int)CD11c(+)) DCs increased on days 14 and 21. Similar changes in both migratory and resident DCs were also detected on day 14 in MLN of TNFRp55(-/-) mice. In vitro, LPS-stimulated migratory TNFRp55(-/-) DCs of MLN increased IL-12/23p40 compared with wild-type mice. In addition, TNFRp55(-/-) bone marrow-derived DCs in a TNFRp55(-/-) MLN microenvironment exhibited higher expression of CCR7 after Y. enterocolitica infection. The major intestinal DC subsets (CD103(+)CD11b(-), CD103(-)CD11b(+), and CD103(+)CD11b(+)) were found in the RLN of Y. enterocolitica-infected TNFRp55(-/-) mice. Fingolimod (FTY720) treatment of Y. enterocolitica-infected mice reduced the CD11b(-) subset of migratory DCs in RLN of TNFRp55(-/-) mice and significantly suppressed the severity of ReA in these mice. This result was associated with decreased articular IL-12/23p40 and IFN-gamma 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. CI - Copyright (c) 2020 by The American Association of Immunologists, Inc. FAU - Silva, Juan E AU - Silva JE AD - Facultad de Quimica, Bioquimica y Farmacia, Universidad Nacional de San Luis, 5700 San Luis, Argentina; and. AD - Instituto Multidisciplinario de Investigaciones Biologicas-San Luis, Consejo Nacional de Investigaciones Cientificas y Tecnicas-Universidad Nacional de San Luis, 5700 San Luis, Argentina. FAU - Mayordomo, Andrea C AU - Mayordomo AC AUID- ORCID: 0000-0002-0399-9644 AD - Instituto Multidisciplinario de Investigaciones Biologicas-San Luis, Consejo Nacional de Investigaciones Cientificas y Tecnicas-Universidad Nacional de San Luis, 5700 San Luis, Argentina. FAU - Dave, Mabel N AU - Dave MN AD - Instituto Multidisciplinario de Investigaciones Biologicas-San Luis, Consejo Nacional de Investigaciones Cientificas y Tecnicas-Universidad Nacional de San Luis, 5700 San Luis, Argentina. FAU - Aguilera Merlo, Claudia AU - Aguilera Merlo C AD - Facultad de Quimica, Bioquimica y Farmacia, Universidad Nacional de San Luis, 5700 San Luis, Argentina; and. FAU - Elicabe, Ricardo J AU - Elicabe RJ AD - Facultad de Quimica, Bioquimica y Farmacia, Universidad Nacional de San Luis, 5700 San Luis, Argentina; and. AD - Instituto Multidisciplinario de Investigaciones Biologicas-San Luis, Consejo Nacional de Investigaciones Cientificas y Tecnicas-Universidad Nacional de San Luis, 5700 San Luis, Argentina. FAU - Di Genaro, Maria S AU - Di Genaro MS AUID- ORCID: 0000-0001-9854-5786 AD - Facultad de Quimica, Bioquimica y Farmacia, Universidad Nacional de San Luis, 5700 San Luis, Argentina; and sdigena@unsl.edu.ar. AD - Instituto Multidisciplinario de Investigaciones Biologicas-San Luis, Consejo Nacional de Investigaciones Cientificas y Tecnicas-Universidad Nacional de San Luis, 5700 San Luis, Argentina. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200302 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (PHB2 protein, human) RN - 0 (Prohibitins) RN - 0 (Receptors, Tumor Necrosis Factor, Type I) RN - 0 (Tumor Necrosis Factor Decoy Receptors) RN - 1IEO802L3J (recombinant human tumor necrosis factor-binding protein-1) SB - IM MH - Animals MH - Arthritis, Reactive/*immunology/metabolism MH - Dendritic Cells/*immunology/metabolism MH - Lymph Nodes/*immunology/metabolism MH - Male MH - Mesentery/*immunology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Prohibitins MH - Receptors, Tumor Necrosis Factor, Type I/immunology/*metabolism MH - Signal Transduction/immunology MH - Tumor Necrosis Factor Decoy Receptors/immunology/*metabolism MH - Yersinia Infections/*immunology/metabolism MH - Yersinia enterocolitica/*immunology EDAT- 2020/03/04 06:00 MHDA- 2020/10/24 06:00 CRDT- 2020/03/04 06:00 PHST- 2019/09/18 00:00 [received] PHST- 2020/01/24 00:00 [accepted] PHST- 2020/03/04 06:00 [pubmed] PHST- 2020/10/24 06:00 [medline] PHST- 2020/03/04 06:00 [entrez] AID - jimmunol.1901137 [pii] AID - 10.4049/jimmunol.1901137 [doi] PST - ppublish SO - J Immunol. 2020 Apr 1;204(7):1859-1868. doi: 10.4049/jimmunol.1901137. Epub 2020 Mar 2.