| First Author | Wu R | Year | 2022 |
| Journal | Nat Immunol | Volume | 23 |
| Issue | 11 | Pages | 1536-1550 |
| PubMed ID | 36271147 | Mgi Jnum | J:333733 |
| Mgi Id | MGI:7440129 | Doi | 10.1038/s41590-022-01324-w |
| Citation | Wu R, et al. (2022) Mechanisms of CD40-dependent cDC1 licensing beyond costimulation. Nat Immunol 23(11):1536-1550 |
| abstractText | CD40 signaling in classical type 1 dendritic cells (cDC1s) is required for CD8 T cell-mediated tumor rejection, but the underlying mechanisms are incompletely understood. Here, we identified CD40-induced genes in cDC1s, including Cd70, Tnfsf9, Ptgs2 and Bcl2l1, and examined their contributions to anti-tumor immunity. cDC1-specific inactivation of CD70 and COX-2, and global CD27 inactivation, only partially impaired tumor rejection or tumor-specific CD8 T cell expansion. Loss of 4-1BB, alone or in Cd27(-/-) mice, did not further impair anti-tumor immunity. However, cDC1-specific CD40 inactivation reduced cDC1 mitochondrial transmembrane potential and increased caspase activation in tumor-draining lymph nodes, reducing migratory cDC1 numbers in vivo. Similar impairments occurred during in vitro antigen presentation by Cd40(-/-) cDC1s to CD8(+) T cells, which were reversed by re-expression of Bcl2l1. Thus, CD40 signaling in cDC1s not only induces costimulatory ligands for CD8(+) T cells but also induces Bcl2l1 that sustains cDC1 survival during priming of anti-tumor responses. |
