title: Oral administration of type-II collagen suppresses IL-17-associated RANKL expression of CD4+ T cells in collagen-induced arthritis.
abstract: The receptor activator of nuclear factor kappaB ligand (RANKL) is an osteoclastogenic mediator, which is mainly expressed by stromal cells and osteoblast. However, T cells can also be an important provider for RANKL in special condition such as autoimmune arthritis. We examined the RANKL expression of hyporesponsive CD4+ T cells induced by oral feeding with type II collagen in collagen-induced arthritis (CIA) mice. The potential of RANKL expression in CD4+ T cells was downregulated in tolerance, as compared with CIA. One of possible explanations for this phenomenon is that CII-specific T cell activation was intrinsically impaired in oral tolerance, which caused suppression of RANKL expression of CD4+ T cells. We also investigated the extrinsic role of cytokine in this process. IL-17, well-known pro-inflammatory cytokine was upregulated in CIA and downregulated in tolerance. IL-17 had a potential to stimulate T cells to express RANKL in dose-dependent manner. IL-17-associated RANKL expression of CD4+ T cells was downregulated in oral tolerance, suggesting that the induction of tolerance ameliorates IL-17-induced RANKL expression of T cells in murine CIA. We also discovered that CIA - T cells could enhance osteoclastogenesis but not oral tolerance - T cells. Oral tolerance might be promising therapeutic option in viewpoints of modulating autoreactivity of CII which can induce not only IL-17 production but also RANKL expression in CD4+ T cells.
authors.affiliation: The Center for Rheumatic Diseases in Kangnam St. Mary's Hospital and Rheumatism Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Ji-Hyeon
authors.initials: JH
authors.lastname: Ju
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.forename: Joo-Youn
authors.initials: JY
authors.lastname: Jhun
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Hye-Joa
authors.initials: HJ
authors.lastname: Oh
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Min
authors.forename: Young-Gyu
authors.initials: YG
authors.lastname: Cho
authors.forename: Seu-Yun
authors.initials: SY
authors.lastname: Hwang
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kwok
authors.forename: Soo-Hong
authors.initials: SH
authors.lastname: Seo
authors.forename: Chong-Hyeon
authors.initials: CH
authors.lastname: Yoon
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D024043:Collagen Type II / Q000008:administration & dosage*; D015870:Gene Expression; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D007596:Joints / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010010:Osteoclasts / Q000166:cytology; D053244:Osteoprotegerin / Q000096:biosynthesis; D053245:RANK Ligand / Q000096:biosynthesis* / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000096:biosynthesis
chemical_list: D017252:CD3 Complex; D024043:Collagen Type II; D020381:Interleukin-17; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D016753:Interleukin-10