The pathogen recognition receptor NOD2 regulates human FOXP3+ T cell survival

Meher K. Rahman, Emilie H. Midtling, Phyllis A. Svingen, Yuning Xiong, Michael P. Bell, Jeanne Tung, Tom Smyrk, Larry J. Egan, William A. Faubion

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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-κB 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.

Original languageEnglish (US)
Pages (from-to)7247-7256
Number of pages10
JournalJournal of Immunology
Volume184
Issue number12
DOIs
StatePublished - Jun 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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