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Classical Flt3L-dependent dendritic cells control immunity to protein vaccine

Authors
 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 
Citation
 JOURNAL OF EXPERIMENTAL MEDICINE, Vol.211(9) : 1875-1891, 2014 
Journal Title
 JOURNAL OF EXPERIMENTAL MEDICINE 
ISSN
 0022-1007 
Issue Date
2014
MeSH
Animals ; Antigen Presentation ; Antigens, Surface/genetics ; Antigens, Surface/immunology ; Dendritic Cells/classification ; Dendritic Cells/immunology* ; Female ; Gene Expression ; Humans ; Immunity, Humoral/genetics ; Injections, Intradermal ; Injections, Subcutaneous ; Interferon-gamma/biosynthesis ; Lectins, C-Type/genetics ; Lectins, C-Type/immunology ; Ligands ; Male ; Mannose-Binding Lectins/genetics ; Mannose-Binding Lectins/immunology ; Membrane Proteins/deficiency ; Membrane Proteins/genetics ; Membrane Proteins/immunology* ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Ovalbumin/immunology ; Proteins/immunology ; T-Lymphocyte Subsets/immunology ; Transcription Factors/immunology ; Vaccines/administration & dosage ; Vaccines/immunology*
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.
Full Text
http://jem.rupress.org/content/211/9/1875.long
DOI
10.1084/jem.20131397
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Chae Gyu(박채규) ORCID logo https://orcid.org/0000-0003-1906-1308
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99662
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