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The pathogen recognition receptor NOD2 regulates human FOXP3+ T cell survival
Meher K Rahman1, Emilie H Midtling, Phyllis A Svingen
1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|May 21, 2010
Summary
Pathogen recognition receptors protect human T regulatory cells from apoptosis in Crohn's disease. NOD2 activation by muramyl dipeptide enhances FOXP3+ T cell survival, crucial for gut immunity.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Pathogen recognition receptors (PRRs) are expressed by human FOXP3+ T regulatory cells, but their function remains unclear.
- FOXP3+ lymphocytes play a critical role in maintaining immune homeostasis, particularly in the gut.
- Crohn's disease, an inflammatory bowel disease, is associated with genetic variations in PRR genes like NOD2.
Purpose of the Study:
- To investigate the function of PRRs in human FOXP3+ T regulatory cells.
- To explore the role of NOD2 signaling in the context of Crohn's disease.
- To determine the impact of NOD2 activation on T regulatory cell survival.
Main Methods:
- Analysis of FOXP3+ lymphocyte quantity in Crohn's disease patients with varying NOD2 genotypes.
- Stimulation of primary human FOXP3+ T cells with the NOD2 ligand, muramyl dipeptide (MDP).
- Assessment of NF-kappaB activation and apoptosis resistance in response to MDP stimulation.
Main Results:
- A deficiency in FOXP3+ lymphocytes was observed in Crohn's disease patients with NOD2 polymorphisms.
- MDP activated NF-kappaB in primary human FOXP3+ T cells.
- MDP-stimulated FOXP3+ T cells exhibited protection against Fas-mediated apoptosis.
- This protective effect was diminished in cells from patients with disease-associated NOD2 polymorphisms.
Conclusions:
- Pathogen recognition receptors, specifically NOD2, play a protective role in human T regulatory cells.
- NOD2 signaling confers resistance to apoptosis in FOXP3+ T cells, potentially in inflammatory environments like the gut.
- Dysfunctional NOD2 signaling may contribute to immune dysregulation in Crohn's disease.
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