The pathogen recognition receptor NOD2 regulates human FOXP3+ T cell survival. J Immunol 2010 Jun 15;184(12):7247-56
Date
05/21/2010Pubmed ID
20483763Pubmed Central ID
PMC3886856DOI
10.4049/jimmunol.0901479Scopus ID
2-s2.0-77953637385 (requires institutional sign-in at Scopus site) 57 CitationsAbstract
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.
Author List
Rahman MK, Midtling EH, Svingen PA, Xiong Y, Bell MP, Tung J, Smyrk T, Egan LJ, Faubion WA JrAuthor
Emilie Regner MD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ApoptosisBlotting, Western
Cell Separation
Cell Survival
Crohn Disease
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Forkhead Transcription Factors
Genotype
Humans
Immunohistochemistry
Intestinal Mucosa
Male
Middle Aged
Nod2 Signaling Adaptor Protein
Polymorphism, Single Nucleotide
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocyte Subsets
T-Lymphocytes, Regulatory
Transfection
