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

TY - JOUR

T1 - CD1d knockout mice exhibit aggravated contact hypersensitivity responses due to reduced interleukin-10 production predominantly by regulatory B cells

AU - Fjelbye, Jonas

AU - Antvorskov, Julie C

AU - Buschard, Karsten

AU - Issazadeh-Navikas, Shohreh

AU - Engkilde, Kåre

N1 - © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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 (Bregs) 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 Bregs.

AB - 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 (Bregs) 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 Bregs.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/exd.12792

DO - 10.1111/exd.12792

M3 - Journal article

C2 - 26121177

SN - 1600-0625

VL - 24

SP - 853

EP - 856

JO - Experimental Dermatology

JF - Experimental Dermatology

IS - 11

ER -