NKT cells promote antibody-induced joint inflammation by suppressing transforming growth factor beta1 production.
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.
Kim
Hye Young
HY
Department of Pathology, College of Medicine, Seoul National University, Seoul, Korea.
Kim
Hyun Jung
HJ
Min
Hye Sook
HS
Kim
Sanghee
S
Park
Weon Seo
WS
Park
Seong Hoe
SH
Chung
Doo Hyun
DH
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*
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D005699:Galactosylceramides; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma