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J Exp Med. 2014 Aug 25;211(9):1875-91. doi: 10.1084/jem.20131397. Epub 2014 Aug 18.

Classical Flt3L-dependent dendritic cells control immunity to protein vaccine.

Author information

1
Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Department of Dermatology/Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, MA 02115 nanandasabapathy@partners.org.
2
Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
3
Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, Hospital Informatics, and Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
4
Department of Dermatology/Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, MA 02115.
5
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, D-55131 Mainz, Germany.

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.

Comment in

PMID:
25135299
PMCID:
PMC4144735
DOI:
10.1084/jem.20131397
[Indexed for MEDLINE]
Free PMC Article

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