Classical Flt3L-dependent dendritic cells control immunity to protein vaccine

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Classical Flt3L-dependent dendritic cells control immunity to protein vaccine

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Title: Classical Flt3L-dependent dendritic cells control immunity to protein vaccine
Author: Anandasabapathy, Niroshana; Feder, Rachel; Mollah, Shamim; Tse, Sze-Wah; Longhi, Maria Paula; Mehandru, Saurabh; Matos, Ines; Cheong, Cheolho; Ruane, Darren; Brane, Lucas; Teixeira, Angela; Dobrin, Joseph; Mizenina, Olga; Park, Chae Gyu; Meredith, Matthew; Clausen, Björn E.; Nussenzweig, Michel C.; Steinman, Ralph M.

Note: Order does not necessarily reflect citation order of authors.

Citation: Anandasabapathy, N., R. Feder, S. Mollah, S. Tse, M. P. Longhi, S. Mehandru, I. Matos, et al. 2014. “Classical Flt3L-dependent dendritic cells control immunity to protein vaccine.” The Journal of Experimental Medicine 211 (9): 1875-1891. doi:10.1084/jem.20131397.
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Abstract: 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.
Published Version: doi:10.1084/jem.20131397
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