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Single-cell and chromatin accessibility profiling reveals regulatory programs of pathogenic Th2 cells in allergic asthma

Author

Listed:
  • Matarr Khan

    (Medical University of Vienna, Center of Pathophysiology, Infectiology and Immunology, Institute of Immunology, Division of Immunobiology)

  • Marlis Alteneder

    (Medical University of Vienna, Center of Pathophysiology, Infectiology and Immunology, Institute of Immunology, Division of Immunobiology)

  • Wolfgang Reiter

    (Max Perutz Labs, Mass Spectrometry Facility, Vienna Biocenter Campus (VBC)
    University of Vienna, Center for Molecular Biology, Department of Biochemistry and Cell Biology)

  • Thomas Krausgruber

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
    Medical University of Vienna, Center for Medical Data Science, Institute of Artificial Intelligence)

  • Lina Dobnikar

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Moritz Madern

    (Medical University of Vienna, Center of Pathophysiology, Infectiology and Immunology, Institute of Immunology, Division of Immunobiology)

  • Monika Waldherr

    (Medical University of Vienna, Center of Pathophysiology, Infectiology and Immunology, Institute of Immunology, Division of Immunobiology
    FH Campus Wien, Department of Applied Life Sciences/Bioengineering/Bioinformatics)

  • Christoph Bock

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
    Medical University of Vienna, Center for Medical Data Science, Institute of Artificial Intelligence)

  • Markus Hartl

    (Max Perutz Labs, Mass Spectrometry Facility, Vienna Biocenter Campus (VBC)
    University of Vienna, Center for Molecular Biology, Department of Biochemistry and Cell Biology)

  • Wilfried Ellmeier

    (Medical University of Vienna, Center of Pathophysiology, Infectiology and Immunology, Institute of Immunology, Division of Immunobiology)

  • Johan Henriksson

    (Umeå University, Umeå Centre for Microbial Research (UCMR), Integrated Science Lab (Icelab), Department of Molecular Biology)

  • Nicole Boucheron

    (Medical University of Vienna, Center of Pathophysiology, Infectiology and Immunology, Institute of Immunology, Division of Immunobiology)

Abstract

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.

Suggested Citation

  • Matarr Khan & Marlis Alteneder & Wolfgang Reiter & Thomas Krausgruber & Lina Dobnikar & Moritz Madern & Monika Waldherr & Christoph Bock & Markus Hartl & Wilfried Ellmeier & Johan Henriksson & Nicole , 2025. "Single-cell and chromatin accessibility profiling reveals regulatory programs of pathogenic Th2 cells in allergic asthma," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57590-3
    DOI: 10.1038/s41467-025-57590-3
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    1. Nicholas Arpaia & Clarissa Campbell & Xiying Fan & Stanislav Dikiy & Joris van der Veeken & Paul deRoos & Hui Liu & Justin R. Cross & Klaus Pfeffer & Paul J. Coffer & Alexander Y. Rudensky, 2013. "Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation," Nature, Nature, vol. 504(7480), pages 451-455, December.
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