Role of invariant natural killer T (iNKT) cells in systemic lupus erythematosus

Mária Godó, Tamás Sessler, P. Hamar

Research output: Article

12 Citations (Scopus)

Abstract

Natural killer T (NKT) cells represent a unique T cell lineage. The NKT cells bearing an invariant TCR (iNKT cells) recognize a small variety of glycolipid antigens in the context of CD1d (non-classical MHC-I) presentation. CD1d-restricted iNKT cells play a regulatory role during an immune response by producing cytokines (IFN-γ, and IL-4). The identification of a-galactosyl-ceramide (α-GalCer), a marine sponge derivative as a potent stimulator of iNKT cells has raised the potential of therapeutic iNKT cell activation. Invariant NKT cells have been implicated in several different autoimmune diseases in mice and humans, including systemic lupus erythematosus (SLE). Abnormalities in the number and functions of NKT cells have been observed in SLE patients and mouse strains genetically predisposed to lupus (MRL/lpr, NZB/W F1). Moreover, inverse correlation between the frequency of NKT cells and IgG levels has been observed. Elevated IgG levels in relatives of patients with lupus as well as in patients with lupus were associated with low frequencies of NKT cells. This review focuses on the potential roles of NKT cells in the pathogenesis of SLE. It summarizes recent advances in glycolipid therapy for murine lupus. First, it has been demonstrated, that repeated administration of α-GalCer to MRL/lpr mice alleviated inflammatory dermatitis but did not influence kidney disease. Treatment of NZB/W mice with α-GalCer resulted in amelioration of SLE symptoms in young mice, but treatment of older animals resulted in disease exacerbation. The effects of NKT cell activation using α -GalCer, on disease progression, were influenced by a variety of parameters, including the genetic background of mice, the α -GalCer dose, number of injections and the stage of the disease process when treatment was performed. Manipulation of NKT cells in the human system may be a promising treatment alternative for the future, however possible deleterious effects have to be carefully investigated first.

Original languageEnglish
Pages (from-to)1778-1787
Number of pages10
JournalCurrent Medicinal Chemistry
Volume15
Issue number18
DOIs
Publication statusPublished - aug. 2008

Fingerprint

Natural Killer T-Cells
T-cells
Systemic Lupus Erythematosus
Glycolipids
Disease Progression
Therapeutics
Immunoglobulin G
Inbred MRL lpr Mouse
Bearings (structural)
Inbred NZB Mouse
Chemical activation
Galactosylceramides
Dermatitis
Kidney Diseases
Porifera
Cell Lineage
Interleukin-4
Autoimmune Diseases

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Role of invariant natural killer T (iNKT) cells in systemic lupus erythematosus. / Godó, Mária; Sessler, Tamás; Hamar, P.

In: Current Medicinal Chemistry, Vol. 15, No. 18, 08.2008, p. 1778-1787.

Research output: Article

Godó, Mária ; Sessler, Tamás ; Hamar, P. / Role of invariant natural killer T (iNKT) cells in systemic lupus erythematosus. In: Current Medicinal Chemistry. 2008 ; Vol. 15, No. 18. pp. 1778-1787.
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