title: FTY720 Abrogates Collagen-Induced Arthritis by Hindering Dendritic Cell Migration to Local Lymph Nodes.
abstract: Because dendritic cells (DCs) play critical roles in the pathogenesis of rheumatoid arthritis, modulation of their functions could serve as a novel therapy. In this study, we demonstrated that FTY720 treatment significantly suppressed the incidence and severity of collagen-induced arthritis (CIA) in DBA/1J mice via the modulation of DC functions. In FTY720-treated CIA mice, a decrease in the number of DCs in local draining lymph nodes (LNs) was observed. In vitro, FTY720 inhibited the trafficking of LPS-stimulated bone marrow-derived DCs (BMDCs). Decreased secretion of CCL19 and downregulation of CCR7 on DCs may explain the mechanisms underlying the impairment of DC migration induced by FTY720. In a DC-induced mouse arthritis model, FTY720 treatment also suppressed the incidence and severity of arthritis, which was correlated with a decrease in the migration of injected BMDCs to draining LNs. Although lower levels of costimulatory molecules (CD40, CD80, and CD86) and I-A(q) expressed on LN DCs were observed in FTY720-treated mice, in vitro analysis showed no effect of FTY720 on LPS-stimulated BMDC maturation. Furthermore, LN cells from FTY720-treated CIA mice displayed diminished production of proinflammatory cytokines in response to collagen II and Con A stimulation. In addition, the ratio of Th1/Th2 in the draining LNs of mice with DC-induced arthritis was decreased upon FTY720 treatment. This finding was consistent with the fact that FTY720 suppressed IL-12p70 production in cultured BMDCs. Taken together, these results indicate that inhibition of DC migration by FTY720 may provide a novel approach in treating autoimmune diseases such as rheumatoid arthritis.
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China 510630; Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, China 510630; Hospital of South China Normal University, Guangzhou, Guangdong, China 510631; and.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China 510630; Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, China 510630;
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China 510630; Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, China 510630;
authors.forename: Qingyou
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China 510630; Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, China 510630;
authors.forename: Hongyu
authors.initials: H
authors.lastname: Jie
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China 510630; Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, China 510630;
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Lao
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China 510630; Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, China 510630;
authors.forename: Jiaochan
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China 510630; Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, China 510630;
authors.forename: Juan
authors.initials: J
authors.lastname: He
authors.affiliation: Hospital of South China Normal University, Guangzhou, Guangdong, China 510631; and.
authors.forename: Xinxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China 510630; Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, China 510630; Department of Urology, No. 421 Hospital of PLA, Guangzhou, Guangdong, China 510010.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Gu
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China 510630; Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, China 510630;
authors.forename: Yi
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China 510630; Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, China 510630; sunew@smu.edu.cn.
authors.forename: Erwei
authors.initials: E
authors.lastname: Sun
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008198:Lymph Nodes / Q000276:immunology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA
chemical_list: D018925:Chemokines; D016207:Cytokines; D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride