title: Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells.
abstract: Foxp3 activity is essential for the normal function of the immune system. Two types of regulatory T (T reg) cells express Foxp3, thymus-generated natural T reg (nT reg) cells, and peripherally generated adaptive T reg (iT reg) cells. These cell types have complementary functions. Until now, it has not been possible to distinguish iT reg from nT reg cells in vivo based solely on surface markers. We report here that Neuropilin 1 (Nrp1) is expressed at high levels by most nT reg cells; in contrast, mucosa-generated iT reg and other noninflammatory iT reg cells express low levels of Nrp1. We found that Nrp1 expression is under the control of TGF-β. By tracing nT reg and iT reg cells, we could establish that some tumors have a very large proportion of infiltrating iT reg cells. iT reg cells obtained from highly inflammatory environments, such as the spinal cords of mice with spontaneous autoimmune encephalomyelitis (EAE) and the lungs of mice with chronic asthma, express Nrp1. In the same animals, iT reg cells in secondary lymphoid organs remain Nrp1(low). We also determined that, in spontaneous EAE, iT reg cells help to establish a chronic phase of the disease.
authors.affiliation: Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Weiss
authors.forename: Angelina M
authors.initials: AM
authors.lastname: Bilate
authors.forename: Michael
authors.initials: M
authors.lastname: Gobert
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: Maria A
authors.initials: MA
authors.lastname: Curotto de Lafaille
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Parkhurst
authors.forename: Huizhong
authors.initials: H
authors.lastname: Xiong
authors.forename: Jayashree
authors.initials: J
authors.lastname: Dolpady
authors.forename: Alan B
authors.initials: AB
authors.lastname: Frey
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ruocco
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Stefan
authors.initials: S
authors.lastname: Floess
authors.forename: Jochen
authors.initials: J
authors.lastname: Huehn
authors.forename: Soyoung
authors.initials: S
authors.lastname: Oh
authors.forename: Ming O
authors.initials: MO
authors.lastname: Li
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Niec
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Rudensky
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dustin
authors.forename: Dan R
authors.initials: DR
authors.lastname: Littman
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lafaille
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D054892:Metagenome / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016212:Transforming Growth Factor beta; D039942:Neuropilin-1