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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.

Original publication

DOI

10.1084/jem.20120914

Type

Journal article

Journal

J Exp Med

Publication Date

24/09/2012

Volume

209

Pages

1723 - S1

Keywords

Animals, Cell Lineage, Cell Membrane, Forkhead Transcription Factors, Gene Expression Regulation, Inflammation, Intestines, Lymphocyte Activation, Lymphocytes, Tumor-Infiltrating, Metagenome, Mice, Mice, Transgenic, Mucous Membrane, Neuropilin-1, T-Lymphocytes, Regulatory, Thymus Gland, Transforming Growth Factor beta