NKT cells inhibit the development of experimental crescentic glomerulonephritis

Hee Yang Seung, Jin Kim Su, Nakkyung Kim, Eun Oh Ji, Gil Lee Jung, Namhyun Chung, Suhnggwon Kim, Su Kim Yon

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

CD1d is an MHC class I-like, β2-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-β1 and decreased phosphorylation of the transcription factors NF-κB and IκB. 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.

Original languageEnglish
Pages (from-to)1663-1671
Number of pages9
JournalJournal of the American Society of Nephrology
Volume19
Issue number9
DOIs
Publication statusPublished - 2008 Sep

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Natural Killer T-Cells
Glomerulonephritis
Glomerular Basement Membrane
Mesangial Cells
Cytoprotection
Adoptive Transfer
Antibodies
Immune System Diseases
Antigen-Presenting Cells
Chemokines
Transcription Factors
Fluorescence
Epithelial Cells
Monoclonal Antibodies
Phosphorylation
Ligands

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

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NKT cells inhibit the development of experimental crescentic glomerulonephritis. / Seung, Hee Yang; Su, Jin Kim; Kim, Nakkyung; Ji, Eun Oh; Jung, Gil Lee; Chung, Namhyun; Kim, Suhnggwon; Yon, Su Kim.

In: Journal of the American Society of Nephrology, Vol. 19, No. 9, 09.2008, p. 1663-1671.

Research output: Contribution to journalArticle

Seung, Hee Yang ; Su, Jin Kim ; Kim, Nakkyung ; Ji, Eun Oh ; Jung, Gil Lee ; Chung, Namhyun ; Kim, Suhnggwon ; Yon, Su Kim. / NKT cells inhibit the development of experimental crescentic glomerulonephritis. In: Journal of the American Society of Nephrology. 2008 ; Vol. 19, No. 9. pp. 1663-1671.
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AU - Kim, Suhnggwon

AU - Yon, Su Kim

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