CD1d deficiency exacerbates inflammatory dermatitis in MRL-lpr/lpr mice.
Mechanisms responsible for the development of autoimmune skin disease in humans and animal models with lupus remain poorly understood. In this study, we have investigated the role of CD1d, an antigen-presenting molecule known to activate natural killer T cells, in the development of inflammatory dermatitis in lupus-susceptible MRL-lpr/lpr mice. In particular, we have established MRL-lpr/lpr mice carrying a germ-line deletion of the CD1d genes. We demonstrate that CD1d-deficient MRL-lpr/lpr mice, as compared with wild-type littermates, have more frequent and more severe skin disease, with increased local infiltration with mast cells, lymphocytes and dendritic cells, including Langerhans cells. CD1d-deficient MRL-lpr/lpr mice had increased prevalence of CD4(+) T cells in the spleen and liver and of TCR alpha beta (+)B220(+) cells in lymph nodes. Furthermore, CD1d deficiency was associated with decreased T cell production of type 2 cytokines and increased or unchanged type 1 cytokines. These findings indicate a regulatory role of CD1d in inflammatory dermatitis. Understanding the mechanisms by which CD1d deficiency results in splenic T cell expansion and cytokine alterations, with increased dermal infiltration of dendritic cells and lymphocytes in MRL-lpr/lpr mice, will have implications for the pathogenesis of inflammatory skin diseases.
Yang
Jun-Qi
JQ
Autoimmunity and Tolerance Laboratory, Department of Internal Medicine, University of Cincinnati, and Veterans Affairs Medical Center, Cincinnati, Ohio 45267, USA.
Chun
Taehoon
T
Liu
Hongzhu
H
Hong
Seokmann
S
Bui
Hai
H
Van Kaer
Luc
L
Wang
Chyung-Ru
CR
Singh
Ram Raj
RR
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D055610:Antigens, CD1d; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003872:Dermatitis / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008099:Liver / Q000276:immunology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D009393:Nephritis / Q000276:immunology; D009929:Organ Size / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma