CD1d knockout mice exhibit aggravated contact hypersensitivity responses due to reduced interleukin-10 production predominantly by regulatory B cells

Exp Dermatol. 2015 Nov;24(11):853-6. doi: 10.1111/exd.12792. Epub 2015 Aug 21.

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) .

Keywords: Bregs; CD1d knockout; NKT cells; contact hypersensitivity; dinitrochlorobenzene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD1d / physiology*
  • B-Lymphocytes, Regulatory / metabolism*
  • Cytokines / blood
  • Dermatitis, Contact / immunology*
  • Dermatitis, Contact / metabolism
  • Dinitrochlorobenzene
  • Immunization
  • Interleukin-10 / metabolism*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells / physiology*
  • Peritoneal Cavity / cytology
  • Skin / immunology
  • Spleen / immunology

Substances

  • Antigens, CD1d
  • CD1d antigen, mouse
  • Cytokines
  • Dinitrochlorobenzene
  • IL10 protein, mouse
  • Interleukin-10