期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 211, 期 9, 页码 1875-1891出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20131397
关键词
-
资金
- National Center for Research Resources, National Institutes of Health (NIH) [RR024142]
- Dermatology Foundation
- NIH [AI40045, 81677, 13013]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR063461-01A1]
- Klarman family foundation grants
- New York Community Trust Frances Florio Fund
- British Heart Foundation [FS/13/49/30421] Funding Source: researchfish
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据