Combined TLR2/TLR4 activation equip non-mucosal dendritic cells to prime Th1 cells with gut tropism

• Published in: iScience 2024-12, Vol.27 (12), p.111232, Article 111232
• Main Authors: Zúquete, Sara, Ferreira, Mariana, Delgado, Inês L.S., Gazalle, Paula, Andaluz, Stephanie, Rosa, Maria Teresa, Mendes, Ana Catarina, Santos, Dulce, Nolasco, Sofia, Graça, Luís, Leitão, Alexandre, Basto, Afonso P.
• Format: Article
• Language: English
• Subjects: biological sciences; immune system; immunology; natural sciences
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.111232

Activated CD4+ T cells located at mucosal surfaces orchestrate local effector immune mechanisms. When properly polarized, these cells contribute to block infections at early stages and may be essential to restrain the local growth of mucosal tumors, playing a critical role in host protection. How CD4+ T cells simultaneously integrate gut-homing instructions and Th polarization signals transmitted by TLR activated dendritic cells (DCs) is unknown. Here, we show that the combined activation through TLR2, which alone does not induce a clear Th polarization, and TLR4, which alone does not imprint mucosal tropism, equip non-mucosal DCs to prime gut-homing CD4+ T cells with reinforced Th1 polarization. These results show that targeting DCs with combined innate stimuli with distinct properties is a rational strategy to program the outcome of T cell polarization and simultaneously control their tissue tropism. Exploring this strategy could enhance the efficacy of vaccines and immune cell therapies. [Display omitted] •Combined TLR2/TLR4 activation induces ALDH activity in non-mucosal DCs•CD4+ T cells primed by TLR2/TLR4 activated DCs co-express IFN-γ and α4β7/CCR9•CD4+ T cells thus primed show an enhanced in vivo tropism to the gut•Subcutaneous immunization with TLR2/TLR4 agonists primes gut-associated Th1 cells Natural sciences, Biological sciences, Immunology, Immune system