Immunoregulatory role of CD1d in the hydrocarbon oil-induced model of lupus nephritis.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is accompanied by the emergence of autoreactive T cells and a reduction in regulatory T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted NK T cells, suggesting a role for these cells in the regulation of SLE. In this study, we show that CD1d deficiency exacerbates lupus nephritis induced by the hydrocarbon oil pristane. This exacerbation in disease is associated with: 1) reduced TNF-alpha and IL-4 production by T cells, especially during the disease induction phase; and 2) expansion of marginal zone B cells. Strikingly, inoculation of pristane in wild-type mice resulted in reduced numbers and/or functions of NK T cells and CD1d-expressing dendritic cells. These findings suggest that CD1d may play an immunoregulatory role in the development of lupus in the pristane-induced model.
Yang
Jun-Qi
JQ
Department of Internal Medicine, Autoimmunity and Tolerance Laboratory, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Singh
Avneesh K
AK
Wilson
Michael T
MT
Satoh
Minoru
M
Stanic
Aleksandar K
AK
Park
Jang-June
JJ
Hong
Seokmann
S
Gadola
Stephan D
SD
Mizutani
Akiei
A
Kakumanu
Srinivasa R
SR
Reeves
Westley H
WH
Cerundolo
Vincenzo
V
Joyce
Sebastian
S
Van Kaer
Luc
L
Singh
Ram Raj
RR
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000502:physiology*; D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000502:physiology*; D055610:Antigens, CD1d; D001323:Autoantibodies / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D005699:Galactosylceramides / Q000494:pharmacology; D017353:Gene Deletion; D007274:Injections, Intraperitoneal; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008181:Lupus Nephritis / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013729:Terpenes / Q000008:administration & dosage / Q000633:toxicity*
D000276:Adjuvants, Immunologic; D018949:Antigens, CD1; D055610:Antigens, CD1d; D001323:Autoantibodies; C526877:CD1D protein, human; D016207:Cytokines; D005699:Galactosylceramides; D013729:Terpenes; C009042:pristane