Classical Flt3L-dependent dendritic cells control immunity to protein vaccine

Niroshana Anandasabapathy, Rachel Feder, Shamim Mollah, Sze Wah Tse, Maria Paula Longhi, Saurabh Mehandru, Ines Matos, Cheolho Cheong, Darren Ruane, Lucas Brane, Angela Teixeira, Joseph Dobrin, Olga Mizenina, Chae Gyu Park, Matthew Meredith, Björn E. Clausen, Michel C. Nussenzweig, Ralph M. Steinman

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

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 Flt3Ldependent, LN-resident cDCs.

Original languageEnglish (US)
Pages (from-to)1875-1891
Number of pages17
JournalJournal of Experimental Medicine
Volume211
Issue number9
DOIs
StatePublished - 2014

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