| First Author | Edwards JP | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 11 | Pages | 5506-15 |
| PubMed ID | 23645881 | Mgi Jnum | J:204761 |
| Mgi Id | MGI:5543327 | Doi | 10.4049/jimmunol.1300199 |
| Citation | Edwards JP, et al. (2013) Regulation of the expression of GARP/latent TGF-beta1 complexes on mouse T cells and their role in regulatory T cell and Th17 differentiation. J Immunol 190(11):5506-15 |
| abstractText | GARP/LRRC32 was defined as a marker of activated human regulatory T cells (Tregs) that is responsible for surface localization of latent TGF-beta1. We find that GARP and latent TGF-beta1 are also found on mouse Tregs activated via TCR stimulation; however, in contrast to human Tregs, GARP is also expressed at a low level on resting Tregs. The expression of GARP can be upregulated on mouse Tregs by IL-2 or IL-4 exposure in the absence of TCR signaling. GARP is expressed at a low level on Tregs within the thymus, and Treg precursors from the thymus concomitantly express GARP and Foxp3 upon exposure to IL-2. The expression of GARP is independent of TGF-beta1 and TGF-beta1 loading into GARP and is independent of furin-mediated processing of pro-TGF-beta1 to latent TGF-beta1. Specific deletion of GARP in CD4(+) T cells results in lack of expression of latent TGF-beta1 on activated Tregs. GARP-deficient Tregs develop normally, are present in normal numbers in peripheral tissues, and are fully competent suppressors of the activation of conventional T cells in vitro. Activated Tregs expressing GARP/latent TGF-beta1 complexes are potent inducers of Th17 differentiation in the presence of exogenous IL-6 and inducers of Treg in the presence of IL-2. Induction of both Th17-producing cells and Tregs is caused preferentially by Tregs expressing the latent TGF-beta1/GARP complex on their cell surface rather than by secreted latent TGF-beta1. |
