The Pathogen Recognition Receptor NOD2 Regulates Human FOXP3+ T Cell Survival

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2010 May 21

PMID 20483763

Citations 35

Authors

Meher K Rahman

Emilie H Midtling

Phyllis A Svingen

Yuning Xiong

Michael P Bell

Jeanne Tung

Tom Smyrk

Larry J Egan

William A Faubion Jr

Affiliations

Soon will be listed here.

Abstract

The expression of pathogen recognition receptors in human FOXP3+ T regulatory cells is established, yet the function of these receptors is currently obscure. In the process of studying the function of both peripheral and lamina propria FOXP3+ lymphocytes in patients with the human inflammatory bowel disease Crohn's disease, we observed a clear deficiency in the quantity of FOXP3+ lymphocytes in patients with disease-associated polymorphisms in the pathogen recognition receptor gene NOD2. Subsequently, we determined that the NOD2 ligand, muramyl dipeptide (MDP), activates NF-kappaB in primary human FOXP3+ T cells. This activation is functionally relevant, as MDP-stimulated human FOXP3+ T cells are protected from death receptor Fas-mediated apoptosis. Importantly, apoptosis protection was not evident in MDP-stimulated FOXP3+ T cells isolated from a patient with the disease-associated polymorphism. Thus, we propose that one function of pathogen recognition receptors in human T regulatory cells is the protection against death receptor-mediated apoptosis in a Fas ligand-rich environment, such as that of the inflamed intestinal subepithelial space.

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