CD1d-dependent NKT cells play a protective role in acute and chronic arthritis models by ameliorating antigen-specific Th1 responses.
A protective and anti-inflammatory role for CD1d-dependent NKT cells (NKTs) has been reported in experimental and human autoimmune diseases. However, their role in arthritis has been unclear, with conflicting reports of CD1d-dependent NKTs acting both as regulatory and disease-promoting cells in arthritis. These differing modes of action might be due to genetic differences of inbred mice and incomplete backcrossing of gene-modified mice. We therefore put special emphasis on controlling the genetic backgrounds of the mice used. Additionally, we used two different murine arthritis models, Ag-induced arthritis (AIA) and collagen-induced arthritis (CIA), to evaluate acute and chronic arthritis in CD1d knockout mice and mice depleted of NK1.1(+) cells. CD1d-deficient mice developed more severe AIA compared with wild-type littermates, with a higher degree of inflammation and proteoglycan depletion. Chronic arthritis in CIA was also worse in the absence of CD1d-dependent NKTs. Elevated levels of Ag-specific IFN-gamma production accompanied these findings rather than changes in IL-17alpha. Depletion of NK1.1(+) cells supported these findings in AIA and CIA. This report provides support for CD1d-dependent NKTs being suppressor cells in acute and chronic arthritis, likely via inhibition of arthritogenic Th1 cells. These results make CD1d-dependent NKTs an attractive target for therapeutic intervention.
Teige
Anna
A
Neuroinflammation Unit, Department of Clinical Sciences, University of Lund, Lund, Sweden.
Bockermann
Robert
R
Hasan
Maruf
M
Olofsson
Katarina E
KE
Liu
Yawei
Y
Issazadeh-Navikas
Shohreh
S
D000208:Acute Disease; D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000502:physiology*; D000950:Antigens, Ly / Q000096:biosynthesis; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology*; D002908:Chronic Disease; D024043:Collagen Type II / Q000633:toxicity; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D007108:Immune Tolerance / Q000235:genetics; D018836:Inflammation Mediators / Q000502:physiology; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000096:biosynthesis; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
D055610:Antigens, CD1d; D000950:Antigens, Ly; C526879:Cd1d1 protein, mouse; D024043:Collagen Type II; D018984:Epitopes, T-Lymphocyte; D018836:Inflammation Mediators; C527211:Klrb1c protein, mouse; D055651:NK Cell Lectin-Like Receptor Subfamily B