title: CD1d knockout mice exhibit aggravated contact hypersensitivity responses due to reduced interleukin-10 production predominantly by regulatory B cells.
abstract: Conflicting observations have been reported concerning the role of CD1d-dependent natural killer T (NKT) cells in contact hypersensitivity (CHS), supporting either a disease-promoting or downregulatory function. We studied the role of NKT cells in CHS by comparing the immune response in CD1d knockout (CD1d KO) and wild-type (Wt) mice after contact allergen exposure. For induction of CHS, C57BL/6 CD1d KO mice (n = 6) and C57BL/6 Wt mice (n = 6) were sensitised with 1% (w/v) dinitrochlorobenzene (DNCB) or vehicle for three consecutive days and subsequently challenged with a single dose of 0.5% DNCB (w/v) on the ears fifteen days later. We demonstrate that CD1d KO mice, as compared with Wt littermates, have more pronounced infiltration of mononuclear cells in the skin (29.1% increase; P < 0.001), lower frequencies of interleukin-10(+) B cells (B(regs) ) in the spleen (53.2% decrease; P < 0.05) and peritoneal cavity (80.8% decrease; P < 0.05) and increased production of interferon-γ (3-fold; P < 0.05) after DNCB sensitisation and challenge, which suggests an important regulatory and protective role of CD1d-dependent NKT cells in CHS in our model, at least in part via regulation of IL-10 producing B(regs) .
authors.affiliation: The Bartholin Institute, Rigshospitalet, Copenhagen Biocenter, Copenhagen, Denmark.
authors.forename: Jonas
authors.initials: J
authors.lastname: Fjelbye
authors.affiliation: The Bartholin Institute, Rigshospitalet, Copenhagen Biocenter, Copenhagen, Denmark.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Antvorskov
authors.affiliation: The Bartholin Institute, Rigshospitalet, Copenhagen Biocenter, Copenhagen, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Buschard
authors.affiliation: Neuroinflammation Unit, Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Shohreh
authors.initials: S
authors.lastname: Issazadeh-Navikas
authors.affiliation: The Bartholin Institute, Rigshospitalet, Copenhagen Biocenter, Copenhagen, Denmark.|Department of Dermato-Allergology, National Allergy Research Centre, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kåre
authors.initials: K
authors.lastname: Engkilde
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000502:physiology*; D060151:B-Lymphocytes, Regulatory / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism; D004137:Dinitrochlorobenzene; D007114:Immunization; D016753:Interleukin-10 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000502:physiology*; D010529:Peritoneal Cavity / Q000166:cytology; D012867:Skin / Q000276:immunology; D013154:Spleen / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; D016207:Cytokines; D004137:Dinitrochlorobenzene; C556062:IL10 protein, mouse; D016753:Interleukin-10
keywords: Bregs; CD1d knockout; NKT cells; contact hypersensitivity; dinitrochlorobenzene