TLR5 activation in respiratory epithelial cells orchestrate mucosal Th17 response through both indirect and direct pathways

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 17, 2025

Flagellin, a potent mucosal adjuvant administered via the intranasal route, has been widely recognized for its capacity to enhance immune responses against diverse pathogens. However, effects and underlying mechanisms by which flagellin modulates CD4+ T cell differentiation remain incompletely understood. Recombinant proteins, including full-length (SF) TLR5-binding deficient variant (SFΔ90–97), were produced purified. An OT-II derived adoptive transfer model, classical immunization model dendritic (DC)-CD4+ co-culturing system used. The proliferation of cells analyzed using flow cytometry analysis. RNA sequencing neutralizing antibody blocking experiments performed determine essential cytokines involved in modulated Th17 differentiation. Flagellin preferentially promotes Respiratory epithelial (RECs), acting as sentinel cells, are first encounter exogenous stimuli during immunization. stimulates secretion various soluble binding TLR5 on surface RECs, with GM-CSF facilitating functional activation airway DCs. GM-CSF-conditioned DCs exhibit upregulated IL-6 expression turn drives polarization naïve toward phenotype. Furthermore, TLR5-regulated REC-derived synergizes TLR5-modulated amplify signals, thereby enhancing induction. induced Th17-enhanced response RECs highlighted roles this process through both indirect direct pathways. For pathway, modulate DC function GM-CSF. Moreover, directly contribute secreting IL-6.

Language: Английский

Nano-Delivery of STING Agonists: Unraveling the Potential of Immunotherapy

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Advancing novel veterinary vaccines: From comprehensive antigen and adjuvant design to preparation process optimization

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 145, P. 113784 - 113784

Published: Dec. 12, 2024

Language: Английский