title: Administration of α-Galactosylceramide Improves Adenine-Induced Renal Injury.
abstract: Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by CD1d. Invariant NKT cells (iNKT) correspond to >90% of the total population of NKTs and reacts to α-galactosylceramide (αGalCer). αGalCer promotes a complex mixture of Th1 and Th2 cytokines, as interferon (IFN)-γ and interleukin (IL)-4. NKT cells and IFN-γ are known to participate in some models of renal diseases, but further studies are still necessary to elucidate their mechanisms. The aim of our study was to analyze the participation of iNKT cells in an experimental model of tubule-interstitial nephritis. We used 8-wk-old C57BL/6j, Jα18KO and IFN-γKO mice. They were fed a 0.25% adenine diet for 10 d. Both adenine-fed wild-type (WT) and Jα18KO mice exhibited renal dysfunction, but adenine-fed Jα18KO mice presented higher expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF)-α and type I collagen. To analyze the role of activated iNKT cells in our model, we administered αGalCer in WT mice during adenine ingestion. After αGalCer injection, we observed a significant reduction in serum creatinine, proinflammatory cytokines and renal fibrosis. However, this improvement in renal function was not observed in IFN-γKO mice after αGalCer treatment and adenine feeding, illustrating that this cytokine plays a role in our model. Our findings may suggest that IFN-γ production is one of the factors contributing to improved renal function after αGalCer administration.
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.|Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil.
authors.forename: Cristhiane Favero
authors.initials: CF
authors.lastname: Aguiar
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Naffah-de-Souza
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil.
authors.forename: Angela
authors.initials: A
authors.lastname: Castoldi
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil.
authors.forename: Matheus
authors.initials: M
authors.lastname: Corrêa-Costa
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil.
authors.forename: Tárcio T
authors.initials: TT
authors.lastname: Braga
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Érika L
authors.initials: ÉL
authors.lastname: Naka
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil.
authors.forename: Mariane T
authors.initials: MT
authors.lastname: Amano
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil.
authors.forename: Débora T R S
authors.initials: DT
authors.lastname: Abate
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil.
authors.forename: Meire I
authors.initials: MI
authors.lastname: Hiyane
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Cenedeze
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.|Instituto Israelita de Ensino e Pesquisa Albert Einstein, Renal Transplantation Unit, Albert Einstein Hospital, São Paulo, Brazil.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pacheco e Silva Filho
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.|Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil.
authors.forename: Niels O S
authors.initials: NO
authors.lastname: Câmara
mesh_terms: D000225:Adenine / Q000633:toxicity; D000818:Animals; D055610:Antigens, CD1d / Q000096:biosynthesis / Q000235:genetics; D024042:Collagen Type I / Q000096:biosynthesis; D005699:Galactosylceramides / Q000008:administration & dosage*; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology; D009393:Nephritis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051437:Renal Insufficiency / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; D024042:Collagen Type I; D005699:Galactosylceramides; C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; C508598:IL4 protein, human; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; C493154:alpha-galactosylceramide; D015847:Interleukin-4; D007371:Interferon-gamma; D000225:Adenine