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 language | English (US) |
|---|---|
| Pages (from-to) | 7247-7256 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 184 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 15 2010 |
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ASJC Scopus subject areas
- Immunology
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - The pathogen recognition receptor NOD2 regulates human FOXP3+ T cell survival
AU - Rahman, Meher K.
AU - Midtling, Emilie H.
AU - Svingen, Phyllis A.
AU - Xiong, Yuning
AU - Bell, Michael P.
AU - Tung, Jeanne
AU - Smyrk, Thomas Christopher
AU - Egan, Larry J.
AU - Faubion, William Alvis
PY - 2010/6/15
Y1 - 2010/6/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.0901479
DO - 10.4049/jimmunol.0901479
M3 - Article
C2 - 20483763
AN - SCOPUS:77953637385
VL - 184
SP - 7247
EP - 7256
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -