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Tissue resident and follicular Treg cell differentiation is regulated by CRAC channels

Author

Listed:
  • Martin Vaeth

    (New York University School of Medicine
    Julius-Maximilians University of Würzburg)

  • Yin-Hu Wang

    (New York University School of Medicine)

  • Miriam Eckstein

    (New York University College of Dentistry
    Julius-Maximilians University of Würzburg)

  • Jun Yang

    (New York University School of Medicine)

  • Gregg J. Silverman

    (New York University School of Medicine)

  • Rodrigo S. Lacruz

    (New York University College of Dentistry)

  • Kasthuri Kannan

    (New York University School of Medicine
    New York University School of Medicine)

  • Stefan Feske

    (New York University School of Medicine)

Abstract

T regulatory (Treg) cells maintain immunological tolerance and organ homeostasis. Activated Treg cells differentiate into effector Treg subsets that acquire tissue-specific functions. Ca2+ influx via Ca2+ release-activated Ca2+ (CRAC) channels formed by STIM and ORAI proteins is required for the thymic development of Treg cells, but its function in mature Treg cells remains unclear. Here we show that deletion of Stim1 and Stim2 genes in mature Treg cells abolishes Ca2+ signaling and prevents their differentiation into follicular Treg and tissue-resident Treg cells. Transcriptional profiling of STIM1/STIM2-deficient Treg cells reveals that Ca2+ signaling regulates transcription factors and signaling pathways that control the identity and effector differentiation of Treg cells. In the absence of STIM1/STIM2 in Treg cells, mice develop a broad spectrum of autoantibodies and fatal multiorgan inflammation. Our findings establish a critical role of CRAC channels in controlling lineage identity and effector functions of Treg cells.

Suggested Citation

  • Martin Vaeth & Yin-Hu Wang & Miriam Eckstein & Jun Yang & Gregg J. Silverman & Rodrigo S. Lacruz & Kasthuri Kannan & Stefan Feske, 2019. "Tissue resident and follicular Treg cell differentiation is regulated by CRAC channels," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08959-8
    DOI: 10.1038/s41467-019-08959-8
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    Cited by:

    1. Juan F. Quintana & Praveena Chandrasegaran & Matthew C. Sinton & Emma M. Briggs & Thomas D. Otto & Rhiannon Heslop & Calum Bentley-Abbot & Colin Loney & Luis de Lecea & Neil A. Mabbott & Annette MacLe, 2022. "Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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