IL-12 from endogenous cDC1, and not vaccine DC, is required for Th1 induction.
Cytokines
Dendritic cells
Immunology
Th1 response
Vaccines
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
21 05 2020
21 05 2020
Historique:
received:
20
11
2019
accepted:
22
04
2020
entrez:
22
5
2020
pubmed:
22
5
2020
medline:
19
5
2021
Statut:
epublish
Résumé
Success of DC vaccines relies on the quality of antigen presentation, costimulation, lymph node migration, and the release of IL-12, in case of Th1 priming. Here, we provide evidence for interaction between the injected vaccine DCs with endogenous lymph node-resident DCs for Th1 induction. While migration of the injected DCs was essential for antigen delivery to the lymph node, the injected DCs contributed only partially to Th0 priming and were unable to instruct Th1 generation. Instead, we provide evidence that the lymph node-resident XCR1+ DCs are activated by the injected DCs to present the cognate antigen and release IL-12 for Th1 polarization. The timing of interactions in the draining lymph nodes appeared step-wise as (a) injected DCs with cognate T cells, (b) injected DCs with bystander DCs, and (c) bystander DCs with T cells. The transcriptome of the bystander DCs showed a downregulation of Treg- and Th2/Th9-inducing genes and self-antigen presentation, as well as upregulation of MHC class II and genes required for Th1 instruction. Together, these data show that injected mature lymph node migratory DCs direct T cell priming and bystander DC activation, but not Th1 polarization, which is mediated by endogenous IL-12p70+XCR1+ resident bystander DCs. Our results are of importance for clinical DC-based vaccinations against tumors where endogenous DCs may be functionally impaired by chemotherapy.
Identifiants
pubmed: 32434994
pii: 135143
doi: 10.1172/jci.insight.135143
pmc: PMC7259537
doi:
pii:
Substances chimiques
Cancer Vaccines
0
Receptors, Chemokine
0
XC chemokine receptor 1, mouse
0
Interleukin-12
187348-17-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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