Classical Flt3L-dependent dendritic cells control immunity to protein vaccine. Academic Article uri icon

Overview

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.

authors

  • 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

publication date

  • August 18, 2014

Research

keywords

  • Dendritic Cells
  • Membrane Proteins
  • Vaccines

Identity

PubMed Central ID

  • PMC4144735

Scopus Document Identifier

  • 84906568561

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2012.03.009

PubMed ID

  • 25135299

Additional Document Info

volume

  • 211

issue

  • 9