Zúquete, SaraFerreira, MarianaDelgado, Inês L.Rosa, Maria teresaMendes, Ana CatarinaSantos, DulceNolasco, SofiaGraça, LuísLeitão, AlexandreBasto, Afonso P.2025-07-022025-07-022025-06Zúquete S, Ferreira M, Delgado IL, Rosa MT, Mendes AC, Nolasco S, et al. Ageing affects the CD4+ T cell polarization and mucosal tropism induced by TLR2/TLR4-activated dendritic cells. J Leukoc Biol. 2025:qiaf096. DOI: 10.1093/jleuko/qiaf096. Epub ahead of print.1938-3673http://hdl.handle.net/10400.21/21944This work was funded by Fundação para a Ciência e Tecnologia (FCT, Portugal) through the projects grants PTDC/CVT-CVT/31840/2017, PTDC/CVT-CVT/4599/2021, 2022.04903.PTDC, LA/P/0059/2020 (AL4AnimalS), and UID/CVT/00276/2019 and UIDB/00276/2020 (CIISA). Funding was also provided by Fundación la Caixa through the project HR22-00741.Toll-like receptor (TLR)2 activation induces aldehyde dehydrogenase enzymes in non-mucosal dendritic cells (DCs), enabling them to metabolize vitamin A into all-trans retinoic acid, which induces the expression of mucosal-homing molecules (α4β7 and CCR9) in the activated T cells. Recently, we have shown that the simultaneous activation of non-mucosal DCs through TLR2 and TLR4 maintains such capacity while reinforcing the polarization of primed CD4+ T cells towards Th1. Here, we observed that TLR2/TLR4 stimulation of aged DCs leads to the production of less TNFα and more IL-10, and that CD4+ T cells primed by those DCs express lower levels of the mucosal homing receptor CCR9 and produce less type-1 (IFNγ) and more type-2 (IL-4 and IL-13) cytokines. These results emphasize the importance of considering the age-related alterations in DC function when developing novel immunomodulation strategies that rely on the DC-T cell crosstalk through stimulation of pattern recognition receptors.engToll-like receptor 2Toll-like receptor 4AgeingDendritic cellsIntestineAgeing affects the CD4+ T cell polarization and mucosal tropism induced by TLR2/TLR4-activated dendritic cellsjournal article10.1093/jleuko/qiaf096