Single-cell and chromatin accessibility profiling reveals regulatory programs of pathogenic Th2 cells in allergic asthma
Lung pathogenic T helper type 2 (pTh2) cells are important in mediating allergic asthma, but fundamental questions remain regarding their heterogeneity and epigenetic regulation. Here we investigate immune regulation in allergic asthma by single-cell RNA sequencing in mice challenged with house dust mite, in the presence and absence of histone deacetylase 1 (HDAC1) function. Our analyses indicate two distinct highly proinflammatory subsets of lung pTh2 cells and pinpoint thymic stromal lymphopoietin (TSLP) and Tumour Necrosis Factor Receptor Superfamily (TNFRSF) members as important drivers to generate pTh2 cells in vitro. Using our in vitro model, we uncover how signalling via TSLP and a TNFRSF member shapes chromatin accessibility at the type 2 cytokine gene loci by modulating HDAC1 repressive function. In summary, we have generated insights into pTh2 cell biology and establish an in vitro model for investigating pTh2 cells that proves useful for discovering molecular mechanisms involved in pTh2-mediated allergic asthma.
Authors
- Moritz Madern (ORCID: https://orcid.org/0000-0001-8593-5785)
- Matarr Khan (ORCID: https://orcid.org/0009-0004-2502-5201)
- Wilfried Ellmeier (ORCID: https://orcid.org/0000-0001-8192-8481)
- Monika Waldherr (ORCID: https://orcid.org/0000-0003-1284-0616)
- Marlis Alteneder
- Thomas Krausgruber (ORCID: https://orcid.org/0000-0002-1374-0329)
- Wolfgang Reiter (ORCID: https://orcid.org/0000-0003-1266-8975)
- Lina Dobnikar (ORCID: https://orcid.org/0000-0002-0616-647X)
- Christoph Bock (ORCID: https://orcid.org/0000-0001-6091-3088)
- Markus Hartl (ORCID: https://orcid.org/0000-0002-4970-7336)
- Nicole Boucheron (ORCID: https://orcid.org/0000-0002-4979-8311)
- Johan Henriksson (ORCID: https://orcid.org/0000-0002-7745-2844)
Institutions
- University of Vienna (AT)
- Austrian Academy of Sciences (AT)
- Austrian Research Institute for Artificial Intelligence (AT)
- Max Perutz Labs (AT)
- Hochschule Campus Wien (AT)
- CeMM Research Center for Molecular Medicine (AT)
- Vienna Biocenter (AT)
- Medical University of Vienna (AT)
- Umeå University (SE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-15
- DOI
- https://doi.org/10.1038/s41467-025-57590-3
- Citations
- 8
- Primary Topic
- IL-33, ST2, and ILC Pathways
- Type
- article
- Field-Weighted Citation Impact
- 6.38
Funders
- Austrian Science Fund
- Cancerfonden
- Vetenskapsrådet