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Publication : Rapid and Efficient Generation of Regulatory T Cells to Commensal Antigens in the Periphery.

First Author  Nutsch K Year  2016
Journal  Cell Rep Volume  17
Issue  1 Pages  206-220
PubMed ID  27681432 Mgi Jnum  J:240570
Mgi Id  MGI:5887174 Doi  10.1016/j.celrep.2016.08.092
Citation  Nutsch K, et al. (2016) Rapid and Efficient Generation of Regulatory T Cells to Commensal Antigens in the Periphery. Cell Rep 17(1):206-20
abstractText  Commensal bacteria shape the colonic regulatory T (Treg) cell population required for intestinal tolerance. However, little is known about this process. Here, we use the transfer of naive commensal-reactive transgenic T cells expressing colonic Treg T cell receptors (TCRs) to study peripheral Treg (pTreg) cell development in normal hosts. We found that T cells were activated primarily in the distal mesenteric lymph node. Treg cell induction was rapid, generating >40% Foxp3(+) cells 1 week after transfer. Contrary to prior reports, Foxp3(+) cells underwent the most cell divisions, demonstrating that pTreg cell generation can be the dominant outcome from naive T cell activation. Moreover, Notch2-dependent, but not Batf3-dependent, dendritic cells were involved in Treg cell selection. Finally, neither deletion of the conserved nucleotide sequence 1 (CNS1) region in Foxp3 nor blockade of TGF-beta (transforming growth factor-beta)-receptor signaling completely abrogated Foxp3 induction. Thus, these data show that pTreg cell selection to commensal bacteria is rapid, is robust, and may be specified by TGF-beta-independent signals.
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