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#19443 : Unlocking the respiratory epithelial microenvironment: investigating the role of AhR pathway in respiratory viral pathogenesis.
Topics: Single Cells
Origin: IP
Project type: Expertise

Name of Applicant: Delphine Planas
Date of application: 07-03-2025
Unit: Virus and Immunity
Location: LWOFF 4E 421
Phone: 01 53 55 18 04
@ Mail: delphine.planas@pasteur.fr
@ PI-Mail: olivier.schwartz@pasteur.fr

Project context and summary:

The COVID-19 pandemic highlights the ongoing challenges in managing respiratory outbreaks. The respiratory tract is composed of heterogeneous epithelial structures and numerous specialized cell types 1. Conventional cell lines poorly recapitulate the complexity of the respiratory tract epithelium. This emphasizes the need for physiologically relevant models enabling the recreation of the epithelial microenvironment in vitro to facilitate understanding of biological function and the development of tailored therapeutics.

Our previous bulk RNAseq findings in hNECs show a significant upregulation of AhR expression following viral infection (Fonseca BF et al., unpublished data). Nevertheless, this initial analysis is insufficient for addressing how AhR is modulated across diverse cell populations such as those found in the respiratory epithelia. Therefore, our objective is to perform scRNAseq analysis to: 1) identify which specific cell type express AhR and related pathway components; 2) investigate the transcriptional changes induced by AhR antagonism; 3) examine the impact of AhR antagonism on other inflammatory pathways (e.g. NF-kB, IFN among others); 4) investigate the interplay between diverse cell types in this context. Understanding AhR antagonism under uninfected conditions serves as the basis for further exploration of this pathway during viral infections.


Related team publications:
Planas, D. et al. Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion. Nat Commun 15, 2254 (2024). https://doi.org:10.1038/s41467-024-46490-7
Fonseca BF, Chakrabarti LA. A close shave: How SARS-CoV-2 induces the loss of cilia. J Cell Biol. 2022 Jul 4;221(7):e202206023. doi: 10.1083/jcb.202206023. Epub 2022 Jun 13. PMID: 35695891; PMCID: PMC9198720.
Service Delivery
Manager: marc.monot@pasteur.fr
Status: Kick-off meeting


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