Regulatory T cells (Tregs) represent a major force for immune control and the prevention of excessive or self-directed responses. These cells are marked by expression of the transcription factor Foxp3 and their ability to suppress leukocyte activation. Deficits in Treg function or numbers result in immune mediated pathologies, reflecting their importance as a layer of immune regulation. However the factors and mechanisms responsible for maintaining these cells are incompletely understood. Here, we report that a GPI-anchored molecule known as neuritin is highly and uniquely expressed by Treg and this molecule potently drives expansion and persistence of the ‘Treg-pool’. Transgenic expression of neuritin by Tregs enhanced their division in vitro while treatment with anti-neuritin antibody stunted Treg proliferation. Further suggesting a role in maintaining the Treg population, neuritin transgenic mice displayed expedited recovery in the EAE model of autoimmune disease accompanied by elevated frequencies of Foxp3+ Tregs. Conversely, antibody mediated neuritin blockade prolonged disease and stunted proliferation of Foxp3+ cells during EAE. Further dissection of neuritin activity revealed the involvement of paradoxically enhanced IL-2 production by this Treg specific factor. In all these findings strongly implicate neuritin as a Treg derived factor responsible for the persistence of these cells and their control of immune responses.
- Copyright © 2013 by The American Association of Immunologists, Inc.