Hye Young Kim1,2, Hyun Jung Kim1,2, Hye Sook Min1, Sanghee Kim4, Weon Seo Park5, Seong Hoe Park1,2, and Doo Hyun Chung1,2,3
1 Department of Pathology, College of Medicine
2 Graduate School of Immunology, College of Medicine
3 Rheumatism Research Center, College of Medicine
4 Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 110-799, Korea
5 Division of Specific Organ Cancers, National Cancer Center, Gyeanggi-Do 411-069, Korea
CORRESPONDENCE Doo Hyun Chung
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 -galactosyl ceramide, a potent NKT cell activator, aggravated arthritis. In CD1d-/- mice, transforming growth factor (TGF)-ß1 was found to be elevated in joint tissues, and the blockade of TGF-ß1 using neutralizing monoclonal antibodies restored arthritis. The administration of recombinant TGF-ß1 into C57BL/6 mice reduced joint inflammation. Moreover, the adoptive transfer of NKT cells into CD1d-/- mice restored arthritis and reduced TGF-ß1 production. In vitro assay demonstrated that interleukin (IL)-4 and interferon (IFN)- were involved in suppressing TGF-ß1 production in joint cells. The adoptive transfer of NKT cells from IL-4-/- or IFN--/- mice did not reverse arthritis and TGF-ß1 production in CD1d-/- mice. In conclusion, NKT cells producing IL-4 and IFN- play a role in immune complex-induced joint inflammation by regulating TGF-ß1.