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Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination

Germinal centres (GCs) are T follicular helper cell (Tfh)-dependent structures that form in response to vaccination, producing long-lived antibody secreting plasma cells and memory B cells that protect against subsequent infection. With advancing age the GC and Tfh cell response declines, resulting...

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Autores principales: Stebegg, Marisa, Bignon, Alexandre, Hill, Danika Lea, Silva-Cayetano, Alyssa, Krueger, Christel, Vanderleyden, Ine, Innocentin, Silvia, Boon, Louis, Wang, Jiong, Zand, Martin S, Dooley, James, Clark, Jonathan, Liston, Adrian, Carr, Edward, Linterman, Michelle A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093110/
https://www.ncbi.nlm.nih.gov/pubmed/32204792
http://dx.doi.org/10.7554/eLife.52473
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author Stebegg, Marisa
Bignon, Alexandre
Hill, Danika Lea
Silva-Cayetano, Alyssa
Krueger, Christel
Vanderleyden, Ine
Innocentin, Silvia
Boon, Louis
Wang, Jiong
Zand, Martin S
Dooley, James
Clark, Jonathan
Liston, Adrian
Carr, Edward
Linterman, Michelle A
author_facet Stebegg, Marisa
Bignon, Alexandre
Hill, Danika Lea
Silva-Cayetano, Alyssa
Krueger, Christel
Vanderleyden, Ine
Innocentin, Silvia
Boon, Louis
Wang, Jiong
Zand, Martin S
Dooley, James
Clark, Jonathan
Liston, Adrian
Carr, Edward
Linterman, Michelle A
author_sort Stebegg, Marisa
collection PubMed
description Germinal centres (GCs) are T follicular helper cell (Tfh)-dependent structures that form in response to vaccination, producing long-lived antibody secreting plasma cells and memory B cells that protect against subsequent infection. With advancing age the GC and Tfh cell response declines, resulting in impaired humoral immunity. We sought to discover what underpins the poor Tfh cell response in ageing and whether it is possible to correct it. Here, we demonstrate that older people and aged mice have impaired Tfh cell differentiation upon vaccination. This deficit is preceded by poor activation of conventional dendritic cells type 2 (cDC2) due to reduced type 1 interferon signalling. Importantly, the Tfh and cDC2 cell response can be boosted in aged mice by treatment with a TLR7 agonist. This demonstrates that age-associated defects in the cDC2 and Tfh cell response are not irreversible and can be enhanced to improve vaccine responses in older individuals.
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spelling pubmed-70931102020-03-25 Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination Stebegg, Marisa Bignon, Alexandre Hill, Danika Lea Silva-Cayetano, Alyssa Krueger, Christel Vanderleyden, Ine Innocentin, Silvia Boon, Louis Wang, Jiong Zand, Martin S Dooley, James Clark, Jonathan Liston, Adrian Carr, Edward Linterman, Michelle A eLife Immunology and Inflammation Germinal centres (GCs) are T follicular helper cell (Tfh)-dependent structures that form in response to vaccination, producing long-lived antibody secreting plasma cells and memory B cells that protect against subsequent infection. With advancing age the GC and Tfh cell response declines, resulting in impaired humoral immunity. We sought to discover what underpins the poor Tfh cell response in ageing and whether it is possible to correct it. Here, we demonstrate that older people and aged mice have impaired Tfh cell differentiation upon vaccination. This deficit is preceded by poor activation of conventional dendritic cells type 2 (cDC2) due to reduced type 1 interferon signalling. Importantly, the Tfh and cDC2 cell response can be boosted in aged mice by treatment with a TLR7 agonist. This demonstrates that age-associated defects in the cDC2 and Tfh cell response are not irreversible and can be enhanced to improve vaccine responses in older individuals. eLife Sciences Publications, Ltd 2020-03-24 /pmc/articles/PMC7093110/ /pubmed/32204792 http://dx.doi.org/10.7554/eLife.52473 Text en © 2020, Stebegg et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Stebegg, Marisa
Bignon, Alexandre
Hill, Danika Lea
Silva-Cayetano, Alyssa
Krueger, Christel
Vanderleyden, Ine
Innocentin, Silvia
Boon, Louis
Wang, Jiong
Zand, Martin S
Dooley, James
Clark, Jonathan
Liston, Adrian
Carr, Edward
Linterman, Michelle A
Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination
title Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination
title_full Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination
title_fullStr Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination
title_full_unstemmed Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination
title_short Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination
title_sort rejuvenating conventional dendritic cells and t follicular helper cell formation after vaccination
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093110/
https://www.ncbi.nlm.nih.gov/pubmed/32204792
http://dx.doi.org/10.7554/eLife.52473
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