| First Author | Cao W | Year | 2023 |
| Journal | J Immunol | Volume | 210 |
| Issue | 10 | Pages | 1589-1597 |
| PubMed ID | 37000474 | Mgi Jnum | J:335536 |
| Mgi Id | MGI:7471377 | Doi | 10.4049/jimmunol.2300046 |
| Citation | Cao W, et al. (2023) Tumor Suppressor Adenomatous Polyposis Coli Sustains Dendritic Cell Tolerance through IL-10 in a beta-Catenin-Dependent Manner. J Immunol 210(10):1589-1597 |
| abstractText | Dendritic cells (DC) play important roles in balancing immunity and tolerance, in which beta-catenin signaling plays an important role, yet the underlying mechanisms remain elusive. In this study, we investigated the functions of the tumor suppressor adenomatous polyposis coli (APC), also a key component of the beta-catenin upstream destruction complex in DC. APC depletion in DC does not alter DC and T cell homeostasis under resting conditions. However, APC deficiency in DC leads to attenuated antitumor immunity in mice, which exhibit fewer CD8+ T cells and more Foxp3+ regulatory T cells in tumor and draining lymph nodes. Loss of APC in DC does not affect the expression levels of costimulatory molecules. However, APC-deficient DC produce more IL-10 and exhibit a higher ability of inducing regulatory T cells but a lower ability of priming CD8+ T cells, both of which can be reversed by IL-10 inhibition. Lastly, beta-catenin depletion in APC-deficient DC rescues their antitumor immunity and reverses elevated IL-10 production. Taken together, our results identify that APC drives DC tolerance via the beta-catenin/IL-10 axis. |
