CCR2 enhances CD25 expression by FoxP3(+) regulatory T cells and regulates their abundance independently of chemotaxis and CCR2(+) myeloid cells
- Author(s)
- Zhan, Y; Wang, N; Vasanthakumar, A; Zhang, Y; Chopin, M; Nutt, SL; Kallies, A; Lew, AM;
- Journal Title
- Cellular & Molecular Immunology
- Publication Type
- Journal Article
- Abstract
- A wide array of chemokine receptors, including CCR2, are known to control Treg migration. Here, we report that CCR2 regulates Tregs beyond chemotaxis. We found that CCR2 deficiency reduced CD25 expression by FoxP3(+) Treg cells. Such a change was also consistently present in irradiation chimeras reconstituted with mixed bone marrow from wild-type (WT) and CCR2-/- strains. Thus, CCR2 deficiency resulted in profound loss of CD25(hi) FoxP3(+) Tregs in secondary lymphoid organs as well as in peripheral tissues. CCR2-/- Treg cells were also functionally inferior to WT cells. Interestingly, these changes to Treg cells did not depend on CCR2(+) monocytes/moDCs (the cells where CCR2 receptors are most abundant). Rather, we demonstrated that CCR2 was required for TLR-stimulated, but not TCR- or IL-2-stimulated, CD25 upregulation on Treg cells. Thus, we propose that CCR2 signaling can increase the fitness of FoxP3(+) Treg cells and provide negative feedback to counter the proinflammatory effects of CCR2 on myeloid cells.
- Publisher
- Springer Nature
- Research Division(s)
- Molecular Immunology; Immunology
- PubMed ID
- 30538272
- Publisher's Version
- https://doi.org/10.1038/s41423-018-0187-8
- NHMRC Grants
- NHMRC/1037321, NHMRC/1080321, NHMRC/1105209, NHMRC/1143976,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-01-14 12:35:26
Last Modified: 2019-01-14 03:14:05