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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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/52473 |
| _version_ | 1811202947455909888 |
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| author | Marisa Stebegg Alexandre Bignon Danika Lea Hill Alyssa Silva-Cayetano Christel Krueger Ine Vanderleyden Silvia Innocentin Louis Boon Jiong Wang Martin S Zand James Dooley Jonathan Clark Adrian Liston Edward Carr Michelle A Linterman |
| author_facet | Marisa Stebegg Alexandre Bignon Danika Lea Hill Alyssa Silva-Cayetano Christel Krueger Ine Vanderleyden Silvia Innocentin Louis Boon Jiong Wang Martin S Zand James Dooley Jonathan Clark Adrian Liston Edward Carr Michelle A Linterman |
| author_sort | Marisa Stebegg |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T02:46:15Z |
| format | Article |
| id | doaj.art-6e557012f65f4b2383953252e3bddeca |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:46:15Z |
| publishDate | 2020-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6e557012f65f4b2383953252e3bddeca2022-12-22T03:51:09ZengeLife Sciences Publications LtdeLife2050-084X2020-03-01910.7554/eLife.52473Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccinationMarisa Stebegg0https://orcid.org/0000-0001-8434-8271Alexandre Bignon1Danika Lea Hill2Alyssa Silva-Cayetano3https://orcid.org/0000-0003-0533-1629Christel Krueger4https://orcid.org/0000-0001-5601-598XIne Vanderleyden5Silvia Innocentin6Louis Boon7Jiong Wang8Martin S Zand9James Dooley10Jonathan Clark11Adrian Liston12Edward Carr13https://orcid.org/0000-0001-9343-4593Michelle A Linterman14https://orcid.org/0000-0001-6047-1996Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United KingdomLaboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United KingdomLaboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United KingdomLaboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United KingdomEpigenetics Programme, Babraham Institute, Cambridge, United KingdomLaboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United KingdomLaboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United KingdomBioceros BV, Utrecht, NetherlandsDivision of Nephrology, Department of Medicine and Clinical and Translational Science Institute, University of Rochester Medical Center, Rochester, United StatesDivision of Nephrology, Department of Medicine and Clinical and Translational Science Institute, University of Rochester Medical Center, Rochester, United StatesAutoimmune Genetics Laboratory, VIB and University of Leuven, Leuven, BelgiumBiological Chemistry, Babraham Institute, Cambridge, United KingdomLaboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United KingdomLaboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom; Department of Medicine, University of Cambridge, Cambridge, United KingdomLaboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United KingdomGerminal 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.https://elifesciences.org/articles/52473germinal centre responseageingt follicular helper cellsdendritic cells |
| spellingShingle | Marisa Stebegg Alexandre Bignon Danika Lea Hill Alyssa Silva-Cayetano Christel Krueger Ine Vanderleyden Silvia Innocentin Louis Boon Jiong Wang Martin S Zand James Dooley Jonathan Clark Adrian Liston Edward Carr Michelle A Linterman Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination eLife germinal centre response ageing t follicular helper cells dendritic cells |
| 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 | germinal centre response ageing t follicular helper cells dendritic cells |
| url | https://elifesciences.org/articles/52473 |
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