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Deficiency of 6B11+ invariant NK T-cells in celiac disease
Randall H Grose1, Fiona M Thompson, Adrian G Cummins
1Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, University of Adelaide, Woodville South, SA 5011, Australia.
Insights
Natural killer T-cells (NK T-cells), crucial for immune regulation, are deficient in celiac disease. This study found significantly reduced NK T-cells and impaired cytokine production in celiac patients.
Area of Science:
- Immunology
- Gastroenterology
Background:
- Immunoregulatory NK T-cells play a role in maintaining immune homeostasis.
- Deficiencies in NK T-cells are observed in various autoimmune conditions.
Purpose of the Study:
- To investigate the potential deficiency of immunoregulatory NK T-cells in celiac disease.
- To assess NK T-cell numbers and function in individuals with celiac disease.
Main Methods:
- Flow cytometry was used to identify NK T-cells (CD3+, CD56+) using 6B11 and V alpha 24 markers in peripheral blood.
- Intracellular cytokine production (IL-4, IL-10, IL-13) was analyzed after anti-CD3/CD28 stimulation.
- Real-time PCR quantified V alpha 24 mRNA expression in duodenal biopsies.
Main Results:
- Celiac subjects exhibited a 70% reduction in NK T-cells compared to healthy controls.
- Stimulation of NK T-cells in celiac patients did not lead to the significant increase in IL-4, IL-10, and IL-13 observed in controls.
- V alpha 24 mRNA levels in duodenal biopsies were markedly decreased in celiac subjects (5% of control levels).
Conclusions:
- Immunoregulatory NK T-cells are significantly deficient in celiac disease.
- The functional impairment of NK T-cells in celiac disease may contribute to the disease pathology.
Abstract:
Immunoregulatory NK T-cells are deficient in certain autoimmune diseases. The purpose of this study was to investigate any deficiency of immunoregulatory NK T-cells in celiac disease. NK T-cells were identified by flow cytometry with 6B11 and V alpha 24 markers in blood from 18 normal and 12 celiac subjects. Blood mononuclear cells were stimulated with anti-CD3/CD28 antibodies and intracellular cytokines assessed at 4 h in seven normal and eight celiac subjects. V alpha 24/GAPDH mRNA was quantitated in duodenal biopsies by real time PCR in 17 control and 13 celiac subjects. NK T-cells in celiac subjects were reduced to 30% of those in normal subjects. Intracellular IL-4, IL-10 and IL-13 increased significantly by 33-41% in normal subjects, but did not change in celiac subjects. V alpha 24/GAPDH mRNA from celiac subjects was reduced to 5% of levels in control subjects. We conclude that immunoregulatory NK T-cells are deficient in celiac disease.
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