Epitopes described in "Invariant NKT cells regulate experimental autoimmune uveitis through inhibition of Th17 differentiation."

Article Authors:Keunhee Oh; Ok-Jin Byoun; Don-Il Ham; Yon Su Kim; Dong-Sup Lee
Article Title:Invariant NKT cells regulate experimental autoimmune uveitis through inhibition of Th17 differentiation.
Reference Detail
Reference ID:1021502
Abstract: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 J18(-/-) , mice. Co-cultured NKT cells from either cytokine-deficient (IL-4(-/-) , IL-10(-/-) , or IFN-(-/-) ) 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 J18(-/-) ) demonstrated an increased disease severity, which was reversed by the transfer of WT or cytokine-deficient (IL-4(-/-) , IL-10(-/-) , or IFN-(-/-) ) NKT cells. Our results indicate that invariant NKT cells inhibited autoimmune uveitis predominantly through the cytokine-independent inhibition of Th17 differentiation.
Affiliations:Laboratory of Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea. keunhee1@snu.ac.kr
Reference Type:Literature
PubMed ID:21268009
Journal:Eur J Immunol
Journal Volume:41
Article Pages:392-402
Journal ISSN:1521-4141
Article Chemical List:Antigens, CD1d;Cd1d1 protein, mouse;Cytokines;Eye Proteins;OVA 323-339;Peptide Fragments;Retinol-Binding Proteins;interstitial retinol-binding protein;Interleukin-4;Ovalbumin
Article MeSH List:Adoptive Transfer; Animals; Antigens, CD1d(genetics; metabolism); Autoimmune Diseases(genetics; immunology; metabolism; pathology); CD4-Positive T-Lymphocytes(immunology; metabolism; pathology); Cell Communication(immunology); Cell Count; Cell Differentiation(immunology); Cytokines(genetics; immunology); Disease Models, Animal; Eye(pathology); Eye Proteins(immunology); Interleukin-4(metabolism); Lymphocyte Activation(immunology); Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Natural Killer T-Cells(immunology; metabolism; pathology; transplantation); Ovalbumin(immunology); Peptide Fragments(immunology); Retinol-Binding Proteins(immunology); Th1 Cells(immunology; metabolism); Th17 Cells(immunology; metabolism); Uveitis(genetics; immunology; metabolism; pathology); Vaccination
Curation Last Updated:2016-04-11 21:16:03