TY - JOUR TI - Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination AU - Stebegg, Marisa AU - Bignon, Alexandre AU - Hill, Danika Lea AU - Silva-Cayetano, Alyssa AU - Krueger, Christel AU - Vanderleyden, Ine AU - Innocentin, Silvia AU - Boon, Louis AU - Wang, Jiong AU - Zand, Martin S AU - Dooley, James AU - Clark, Jonathan AU - Liston, Adrian AU - Carr, Edward AU - Linterman, Michelle A A2 - Kurosaki, Tomohiro A2 - Rath, Satyajit VL - 9 PY - 2020 DA - 2020/03/24 SP - e52473 C1 - eLife 2020;9:e52473 DO - 10.7554/eLife.52473 UR - https://doi.org/10.7554/eLife.52473 AB - 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. KW - germinal centre response KW - ageing KW - t follicular helper cells KW - dendritic cells JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -