title: NKT cells promote antibody-induced joint inflammation by suppressing transforming growth factor beta1 production.
abstract: Although NKT cells has been known to exert protective roles in the development of autoimmune diseases, the functional roles of NKT cells in the downstream events of antibody-induced joint inflammation remain unknown. Thus, we explored the functional roles of NKT cells in antibody-induced arthritis using the K/BxN serum transfer model. NKT cell-deficient mice were resistant to the development of arthritis, and wild-type mice administrated with alpha-galactosyl ceramide, a potent NKT cell activator, aggravated arthritis. In CD1d-/- mice, transforming growth factor (TGF)-beta1 was found to be elevated in joint tissues, and the blockade of TGF-beta1 using neutralizing monoclonal antibodies restored arthritis. The administration of recombinant TGF-beta1 into C57BL/6 mice reduced joint inflammation. Moreover, the adoptive transfer of NKT cells into CD1d-/- mice restored arthritis and reduced TGF-beta1 production. In vitro assay demonstrated that interleukin (IL)-4 and interferon (IFN)-gamma were involved in suppressing TGF-beta1 production in joint cells. The adoptive transfer of NKT cells from IL-4-/- or IFN-gamma-/- mice did not reverse arthritis and TGF-beta1 production in CD1d-/- mice. In conclusion, NKT cells producing IL-4 and IFN-gamma play a role in immune complex-induced joint inflammation by regulating TGF-beta1.
authors.affiliation: Department of Pathology, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.forename: Sanghee
authors.initials: S
authors.lastname: Kim
authors.forename: Weon Seo
authors.initials: WS
authors.lastname: Park
authors.forename: Seong Hoe
authors.initials: SH
authors.lastname: Park
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001168:Arthritis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005699:Galactosylceramides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D017931:DNA Primers; D005699:Galactosylceramides; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma