| First Author | Anandasabapathy N | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 9 | Pages | 1875-91 |
| PubMed ID | 25135299 | Mgi Jnum | J:218713 |
| Mgi Id | MGI:5618223 | Doi | 10.1084/jem.20131397 |
| Citation | Anandasabapathy N, et al. (2014) Classical Flt3L-dependent dendritic cells control immunity to protein vaccine. J Exp Med 211(9):1875-91 |
| abstractText | DCs are critical for initiating immunity. The current paradigm in vaccine biology is that DCs migrating from peripheral tissue and classical lymphoid-resident DCs (cDCs) cooperate in the draining LNs to initiate priming and proliferation of T cells. Here, we observe subcutaneous immunity is Fms-like tyrosine kinase 3 ligand (Flt3L) dependent. Flt3L is rapidly secreted after immunization; Flt3 deletion reduces T cell responses by 50%. Flt3L enhances global T cell and humoral immunity as well as both the numbers and antigen capture capacity of migratory DCs (migDCs) and LN-resident cDCs. Surprisingly, however, we find immunity is controlled by cDCs and actively tempered in vivo by migDCs. Deletion of Langerin(+) DC or blockade of DC migration improves immunity. Consistent with an immune-regulatory role, transcriptomic analyses reveals different skin migDC subsets in both mouse and human cluster together, and share immune-suppressing gene expression and regulatory pathways. These data reveal that protective immunity to protein vaccines is controlled by Flt3L-dependent, LN-resident cDCs. |
