| First Author | Yang G | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 20 | Pages | 12858-67 |
| PubMed ID | 25839231 | Mgi Jnum | J:345274 |
| Mgi Id | MGI:6837759 | Doi | 10.1074/jbc.M114.623421 |
| Citation | Yang G, et al. (2015) Thrombospondin-1 (TSP1)-producing B cells restore antigen (Ag)-specific immune tolerance in an allergic environment. J Biol Chem 290(20):12858-67 |
| abstractText | Restoration of the antigen (Ag)-specific immune tolerance in an allergic environment is refractory. B cells are involved in immune regulation. Whether B cells facilitate the generation of Ag-specific immune tolerance in an allergic environment requires further investigation. This paper aims to elucidate the mechanism by which B cells restore the Ag-specific immune tolerance in an allergic environment. In this study, a B cell-deficient mouse model was created by injecting an anti-CD20 antibody. The frequency of tolerogenic dendritic cell (TolDC) was assessed by flow cytometry. The levels of cytokines were determined by enzyme-linked immunosorbent assay. The expression of thrombospondin-1 (TSP1) was assessed by quantitative real-time RT-PCR, Western blotting, and methylation-specific PCR. The results showed that B cells were required in the generation of the TGF-beta-producing TolDCs in mice. B cell-derived TSP1 converted the latent TGF-beta to the active TGF-beta in DCs, which generated TGF-beta-producing TolDCs. Exposure to IL-13 inhibited the expression of TSP1 in B cells by enhancing the TSP1 gene DNA methylation. Treating food allergy mice with Ag-specific immunotherapy and IL-13 antagonists restored the generation of TolDCs and enhanced the effect of specific immunotherapy. In conclusion, B cells play a critical role in the restoration of specific immune tolerance in an allergic environment. Blocking IL-13 in an allergic environment facilitated the generation of TolDCs and enhanced the therapeutic effect of immunotherapy. |
