S-Space College of Medicine/School of Medicine (의과대학/대학원) Pathology (병리학전공) Journal Papers (저널논문_병리학전공)
NKT cells promote antibody-induced joint inflammation by suppressing transforming growth factor beta1 production
- Kim, Hye Young; Kim, Hyun Jung; Min, Hye Sook; Kim, Sanghee; Park, Weon Seo; Park, Seong Hoe; Chung, Doo Hyun
- Issue Date
- Rockefeller University Press
- J. Exp. Med. 2005;201(1):41-47.
- Animals; Antibodies, Monoclonal/metabolism; Arthritis/*etiology/immunology/metabolism; DNA Primers; Enzyme-Linked Immunosorbent Assay; Galactosylceramides/*pharmacology; Interferon-gamma/metabolism; Interleukin-4/metabolism; Killer Cells, Natural/*drug effects/metabolism; Lymphocyte Activation/drug effects; Mice; Mice, Mutant Strains; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocyte Subsets/*drug effects/metabolism; Transforming Growth Factor beta/*metabolism
- 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.
- 0022-1007 (Print)