Zúquete, SaraFerreira, MarianaDelgado, Inês L.S.Rosa, Maria TeresaMendes, Ana CatarinaSantos, DulceNolasco, SofiaGraca, LuisLeitão, AlexandreBasto, Afonso P.2025-09-042025-09-042025-07-010741-5400PURE: 128700252PURE UUID: 5791d496-6a5d-425c-a42f-65ad8870fb84Scopus: 105011375324PubMed: 40576094http://hdl.handle.net/10362/187556Funding was also provided by Fundaci\u00F3n la Caixa through the project HR22-00741. Publisher Copyright: © The Author(s) 2025. Published by Oxford University Press on behalf of Society for Leukocyte Biology.Toll-like receptor (TLR)2 activation induces aldehyde dehydrogenase enzymes in nonmucosal 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 nonmucosal 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.588634engagingdendritic cellsintestinetoll-like receptor 2toll-like receptor 4Immunology and AllergyImmunologyCell Biologyjournal article10.1093/jleuko/qiaf096https://www.scopus.com/pages/publications/105011375324