ADP-ribosylating adjuvant reveals plasticity in cDC1 cells that drive mucosal Th17 cell development and protection against influenza virus infection
(2022) In Mucosal Immunology 15(4). p.745-761- Abstract
Migratory dendritic cells expressing CD103 are the targets for mucosal vaccines. These belong to either of two lineage-restricted subsets, cDC1 or cDC2 cells, which have been linked to priming of functionally distinct CD4 T cells. However, recent studies have identified plasticity in cDC2 cells with overlapping functions with cDC1 cells, while the converse has not been reported. We genetically engineered a vaccine adjuvant platform that targeted the cholera toxin A1 (CTA1) ADP-ribosylating enzyme to CD103+ cDC1 and cDC2 cells using a single-chain antibody (scFv) to CD103. Unexpectedly, intranasal immunization with the CTA1-svFcCD103 adjuvant modified cDC1 cells to effectively prime Th17 cells, a function previously limited to... (More)
Migratory dendritic cells expressing CD103 are the targets for mucosal vaccines. These belong to either of two lineage-restricted subsets, cDC1 or cDC2 cells, which have been linked to priming of functionally distinct CD4 T cells. However, recent studies have identified plasticity in cDC2 cells with overlapping functions with cDC1 cells, while the converse has not been reported. We genetically engineered a vaccine adjuvant platform that targeted the cholera toxin A1 (CTA1) ADP-ribosylating enzyme to CD103+ cDC1 and cDC2 cells using a single-chain antibody (scFv) to CD103. Unexpectedly, intranasal immunization with the CTA1-svFcCD103 adjuvant modified cDC1 cells to effectively prime Th17 cells, a function previously limited to cDC2 cells. In fact, cDC2 cells were dispensible, while cDC1 cells, lacking in Batf3−/− mice, were critical. Following intranasal immunizations isolated cDC1 cells from mLN exclusively promoted Rorgt+ T cells and IL-17, IL-21, and IL-22 production. Strong CD8 T cell responses through antigen cross presentation by cDC1 cells were also observed. Single-cell RNAseq analysis revealed upregulation of Th17-promoting gene signatures in sorted cDC1 cells. Gene expression in isolated cDC2 cells was largely unaffected. Our finding represents a major shift of paradigm as we have documented functional plasticity in cDC1 cells.
(Less)
- author
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Mucosal Immunology
- volume
- 15
- issue
- 4
- pages
- 745 - 761
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:35418673
- scopus:85128221254
- ISSN
- 1933-0219
- DOI
- 10.1038/s41385-022-00510-1
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2022, The Author(s).
- id
- a3912bc3-6011-4669-ac98-ac744e621156
- date added to LUP
- 2022-05-27 16:47:21
- date last changed
- 2024-04-18 12:29:08
@article{a3912bc3-6011-4669-ac98-ac744e621156,
abstract = {{<p>Migratory dendritic cells expressing CD103 are the targets for mucosal vaccines. These belong to either of two lineage-restricted subsets, cDC1 or cDC2 cells, which have been linked to priming of functionally distinct CD4 T cells. However, recent studies have identified plasticity in cDC2 cells with overlapping functions with cDC1 cells, while the converse has not been reported. We genetically engineered a vaccine adjuvant platform that targeted the cholera toxin A1 (CTA1) ADP-ribosylating enzyme to CD103<sup>+</sup> cDC1 and cDC2 cells using a single-chain antibody (scFv) to CD103. Unexpectedly, intranasal immunization with the CTA1-svFcCD103 adjuvant modified cDC1 cells to effectively prime Th17 cells, a function previously limited to cDC2 cells. In fact, cDC2 cells were dispensible, while cDC1 cells, lacking in Batf3−/− mice, were critical. Following intranasal immunizations isolated cDC1 cells from mLN exclusively promoted Rorgt<sup>+</sup> T cells and IL-17, IL-21, and IL-22 production. Strong CD8 T cell responses through antigen cross presentation by cDC1 cells were also observed. Single-cell RNAseq analysis revealed upregulation of Th17-promoting gene signatures in sorted cDC1 cells. Gene expression in isolated cDC2 cells was largely unaffected. Our finding represents a major shift of paradigm as we have documented functional plasticity in cDC1 cells.</p>}},
author = {{Arabpour, Mohammad and Lebrero-Fernandez, Cristina and Schön, Karin and Strömberg, Anneli and Börjesson, Vanja and Lahl, Katharina and Ballegeer, Marlies and Saelens, Xavier and Angeletti, Davide and Agace, William and Lycke, Nils}},
issn = {{1933-0219}},
language = {{eng}},
number = {{4}},
pages = {{745--761}},
publisher = {{Nature Publishing Group}},
series = {{Mucosal Immunology}},
title = {{ADP-ribosylating adjuvant reveals plasticity in cDC1 cells that drive mucosal Th17 cell development and protection against influenza virus infection}},
url = {{http://dx.doi.org/10.1038/s41385-022-00510-1}},
doi = {{10.1038/s41385-022-00510-1}},
volume = {{15}},
year = {{2022}},
}