NKT cells inhibit the development of experimental crescentic glomerulonephritis.
CD1d is an MHC class I-like, beta2-microglobulin-associated protein, constitutively expressed by antigen-presenting cells and some epithelial cells, which is recognized by NKT cells, a subpopulation of T cells. CD1d-dependent NKT cells confer protection in immune-mediated disorders, but whether these cells modulate the development of glomerulonephritis is unknown. Experimental crescentic glomerulonephritis was induced by administering anti-glomerular basement membrane antibodies to NKT cell-deficient (CD1d(-/-)) and wild-type mice. Compared with wild-type mice, NKT cell-deficient mice had an accelerated course of glomerulonephritis measured by renal function and crescent formation, and this was abrogated by adoptive transfer of NKT cells. Reconstitution with NKT cells also attenuated intraglomerular expression of TGF-beta1 and decreased phosphorylation of the transcription factors NF-kappaB and IkappaB. Adopted transfer of fluorescence-labeled NKT cells demonstrated their distribution to glomeruli damaged by anti-glomerular basement membrane antibodies but not to the tubulointerstitium. The chemokine CXCL16, which is the ligand for CXCR6 on NKT cells, was upregulated in glomeruli after induction of glomerulonephritis, and NKT cells were present in the same glomeruli. In vitro, NKT cells inhibited LPS-stimulated proliferation of mesangial cells, an affect that was reduced by co-current treatment with an anti-CXCL16 monoclonal antibody. In summary, these findings highlight the regulatory capacity of CD1d-dependent NKT cells in experimental glomerulonephritis and suggest that CXCL16 is involved in the recruitment of these cells to the site of injury.
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Korea.
Seung Hee
SH
Yang
Su Jin
SJ
Kim
Nakkyung
N
Kim
Ji Eun
JE
Oh
Jung Gil
JG
Lee
Nam Hyun
NH
Chung
Suhnggwon
S
Kim
Yon Su
YS
Kim
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018949:Antigens, CD1 / Q000235:genetics; D055610:Antigens, CD1d; D049109:Cell Proliferation; D002478:Cells, Cultured; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000502:physiology* / Q000637:transplantation
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; D016207:Cytokines; D016328:NF-kappa B; D051550:I-kappa B Kinase