title: Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo.
abstract: Foxp3(+) CD4(+) T helper cells called regulatory T (T reg) cells play a key role in controlling reactivity to self-antigens and onset of autoimmunity. T reg cells either arise in thymus and are called natural T reg (nT reg) cells or are generated in the periphery through induction of Foxp3 and are called inducible T reg (iT reg) cells. The relative contributions of iT reg cells and nT reg cells in peripheral tolerance remain unclear as a result of an inability to separate these two subsets of T reg cells. Using a combination of novel TCR transgenic mice with a defined self-antigen specificity and conventional mouse models, we demonstrate that a cell surface molecule, neuropilin-1 (Nrp-1), is expressed at high levels on nT reg cells and can be used to separate nT reg versus iT reg cells in certain physiological settings. In addition, iT reg cells generated through antigen delivery or converted under homeostatic conditions lack Nrp-1 expression. Nrp-1(lo) iT reg cells show similar suppressive activity to nT reg cells in controlling ongoing autoimmune responses under homeostatic conditions. In contrast, their activity might be compromised in certain lymphopenic settings. Collectively, our data show that Nrp-1 provides an excellent marker to distinguish distinct T reg subsets and will be useful in studying the role of nT reg versus iT reg cells in different disease settings.
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94122, USA.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Yadav
authors.forename: Cedric
authors.initials: C
authors.lastname: Louvet
authors.forename: Dan
authors.initials: D
authors.lastname: Davini
authors.forename: James M
authors.initials: JM
authors.lastname: Gardner
authors.forename: Marc
authors.initials: M
authors.lastname: Martinez-Llordella
authors.forename: Samantha
authors.initials: S
authors.lastname: Bailey-Bucktrout
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Anthony
authors.forename: Francis M
authors.initials: FM
authors.lastname: Sverdrup
authors.forename: Richard
authors.initials: R
authors.lastname: Head
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kuster
authors.forename: Peter
authors.initials: P
authors.lastname: Ruminski
authors.forename: David
authors.initials: D
authors.lastname: Weiss
authors.forename: David
authors.initials: D
authors.lastname: Von Schack
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
mesh_terms: D000818:Animals; D015551:Autoimmunity; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation / Q000235:genetics; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D039942:Neuropilin-1