title: Peripherally induced human regulatory T cells uncouple Kv1.3 activation from TCR-associated signaling.
abstract: Peripherally induced Tregs (iTregs) are being recognized as a functional and physiologically relevant T-cell subset. Understanding the molecular basis of their development is a necessary step before the therapeutic potential of iTreg manipulation can be exploited. In this study, we report that the differentiation of primary human T cells to suppressor iTregs involves the relocation of key proximal TCR signaling elements to the highly active IL-2-Receptor (IL-2-R) pathway. In addition to the recruitment of lymphocyte-specific protein tyrosine kinase (Lck) to the IL-2-R complex, we identified the dissociation of the voltage-gated K(+)  channel Kv1.3 from the TCR pathway and its functional coupling to the IL-2-R. The regulatory switch of Kv1.3 activity in iTregs may constitute an important contributing factor in the signaling rewiring associated with the development of peripheral human iTregs and sheds new light upon the reciprocal crosstalk between the TCR and the IL-2-R pathways.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Reneer
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Estes
authors.forename: Alejandra C
authors.initials: AC
authors.lastname: Vélez-Ortega
authors.forename: Andrea
authors.initials: A
authors.lastname: Norris
authors.forename: Michael
authors.initials: M
authors.lastname: Mayer
authors.forename: Francesc
authors.initials: F
authors.lastname: Marti
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation; D051664:Kv1.3 Potassium Channel / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018408:Patch-Clamp Techniques; D020239:Receptor Cross-Talk / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D051664:Kv1.3 Potassium Channel; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2