Combined TLR2/TLR4 Activation Equip Non-mucosal Dendritic Cells to Prime Th1 Cells with Gut Tropism

Overview

Journal iScience

Publisher Cell Press

Date 2025 Jan 6

PMID 39759015

Authors

Sara Zuquete

Mariana Ferreira

Ines L S Delgado

Paula Gazalle

Stephanie Andaluz

Maria Teresa Rosa

Ana Catarina Mendes

Dulce Santos

Sofia Nolasco

Luis Graca

Alexandre Leitao

Afonso P Basto

Affiliations

Soon will be listed here.

Abstract

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.

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