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, Thomas Christopher Smyrk, Larry J. Egan, William Alvis Faubion

Research output: Contribution to journalArticle

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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

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Acetylmuramyl-Alanyl-Isoglutamine
Cell Survival
T-Lymphocytes
Death Domain Receptors
Apoptosis
Lymphocytes
Fas Ligand Protein
Cytoprotection
Regulatory T-Lymphocytes
Inflammatory Bowel Diseases
Crohn Disease
Mucous Membrane
Cell Death
human NOD2 protein
Ligands
Genes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Rahman, M. K., Midtling, E. H., Svingen, P. A., Xiong, Y., Bell, M. P., Tung, J., ... Faubion, W. A. (2010). The pathogen recognition receptor NOD2 regulates human FOXP3+ T cell survival. Journal of Immunology, 184(12), 7247-7256. https://doi.org/10.4049/jimmunol.0901479

The pathogen recognition receptor NOD2 regulates human FOXP3+ T cell survival. / Rahman, Meher K.; Midtling, Emilie H.; Svingen, Phyllis A.; Xiong, Yuning; Bell, Michael P.; Tung, Jeanne; Smyrk, Thomas Christopher; Egan, Larry J.; Faubion, William Alvis.

In: Journal of Immunology, Vol. 184, No. 12, 15.06.2010, p. 7247-7256.

Research output: Contribution to journalArticle

Rahman, MK, Midtling, EH, Svingen, PA, Xiong, Y, Bell, MP, Tung, J, Smyrk, TC, Egan, LJ & Faubion, WA 2010, 'The pathogen recognition receptor NOD2 regulates human FOXP3+ T cell survival', Journal of Immunology, vol. 184, no. 12, pp. 7247-7256. https://doi.org/10.4049/jimmunol.0901479
Rahman MK, Midtling EH, Svingen PA, Xiong Y, Bell MP, Tung J et al. The pathogen recognition receptor NOD2 regulates human FOXP3+ T cell survival. Journal of Immunology. 2010 Jun 15;184(12):7247-7256. https://doi.org/10.4049/jimmunol.0901479
Rahman, Meher K. ; Midtling, Emilie H. ; Svingen, Phyllis A. ; Xiong, Yuning ; Bell, Michael P. ; Tung, Jeanne ; Smyrk, Thomas Christopher ; Egan, Larry J. ; Faubion, William Alvis. / The pathogen recognition receptor NOD2 regulates human FOXP3+ T cell survival. In: Journal of Immunology. 2010 ; Vol. 184, No. 12. pp. 7247-7256.
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