Invariant NKT cells regulate experimental autoimmune uveitis through inhibition of Th17 differentiation

Laboratory of Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
European Journal of Immunology (Impact Factor: 4.03). 02/2011; 41(2):392-402. DOI: 10.1002/eji.201040569
Source: PubMed


Although NKT cells have been implicated in diverse immunomodulatory responses, the effector mechanisms underlying the NKT cell-mediated regulation of pathogenic T helper cells are not well understood. Here, we show that invariant NKT cells inhibited the differentiation of CD4(+) T cells into Th17 cells both in vitro and in vivo. The number of IL-17-producing CD4(+) T cells was reduced following co-culture with purified NK1.1(+) TCR(+) cells from WT, but not from CD1d(-/-) or Jα18(-/-) , mice. Co-cultured NKT cells from either cytokine-deficient (IL-4(-/-) , IL-10(-/-) , or IFN-γ(-/-) ) or WT mice efficiently inhibited Th17 differentiation. The contact-dependent mechanisms of NKT cell-mediated regulation of Th17 differentiation were confirmed using transwell co-culture experiments. On the contrary, the suppression of Th1 differentiation was dependent on IL-4 derived from the NKT cells. The in vivo regulatory capacity of NKT cells on Th17 cells was confirmed using an experimental autoimmune uveitis model induced with human IRBP(1-20) (IRBP, interphotoreceptor retinoid-binding protein) peptide. NKT cell-deficient mice (CD1d(-/-) or Jα18(-/-) ) demonstrated an increased disease severity, which was reversed by the transfer of WT or cytokine-deficient (IL-4(-/-) , IL-10(-/-) , or IFN-γ(-/-) ) NKT cells. Our results indicate that invariant NKT cells inhibited autoimmune uveitis predominantly through the cytokine-independent inhibition of Th17 differentiation.

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    • "- cardo et al . , 2009 ) . However several mechanisms shown to be involved in the pathogenesis of autoimmune diseases still need to be investigated in WAS . iNKT cells have been shown to prevent autoimmune disease in a mouse model of experimental Autoim - mune Encephalomyelitis ( EAE ; Miyamoto et al . , 2001 ; Singh et al . , 2001 ) and uveitis ( Oh et al . , 2011 ) . Although the mechanisms have not been fully understood , it has been shown that iNKT activation reduces autoimmune symptoms by limiting the devel - opment of Th17 cells in a cell contact - and cytokine - dependent manner ( Mars et al . , 2009 ) . Moreover , in mice , iNKT cells sup - press anti - DNA antibody production and reduce a"
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