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

Martin Vaeth, Yin Hu Wang, Miriam Eckstein, Jun Yang, Gregg J. Silverman, Rodrigo Lacruz, Kasthuri Kannan, Stefan Feske

Research output: Contribution to journalArticle

Abstract

T regulatory (Treg) cells maintain immunological tolerance and organ homeostasis. Activated Treg cells differentiate into effector Treg subsets that acquire tissue-specific functions. Ca 2+ influx via Ca 2+ release-activated Ca 2+ (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 Ca 2+ signaling and prevents their differentiation into follicular Treg and tissue-resident Treg cells. Transcriptional profiling of STIM1/STIM2-deficient Treg cells reveals that Ca 2+ 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.

Original languageEnglish (US)
Article number1183
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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Regulatory T-Lymphocytes
Cell Differentiation
Tissue
cells
effectors
Set theory
Autoantibodies
Transcription Factors
homeostasis
deletion
organs
set theory
mice
Homeostasis
Inflammation

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Tissue resident and follicular Treg cell differentiation is regulated by CRAC channels. / Vaeth, Martin; Wang, Yin Hu; Eckstein, Miriam; Yang, Jun; Silverman, Gregg J.; Lacruz, Rodrigo; Kannan, Kasthuri; Feske, Stefan.

In: Nature Communications, Vol. 10, No. 1, 1183, 01.12.2019.

Research output: Contribution to journalArticle

Vaeth, M, Wang, YH, Eckstein, M, Yang, J, Silverman, GJ, Lacruz, R, Kannan, K & Feske, S 2019, 'Tissue resident and follicular Treg cell differentiation is regulated by CRAC channels', Nature Communications, vol. 10, no. 1, 1183. https://doi.org/10.1038/s41467-019-08959-8
Vaeth, Martin ; Wang, Yin Hu ; Eckstein, Miriam ; Yang, Jun ; Silverman, Gregg J. ; Lacruz, Rodrigo ; Kannan, Kasthuri ; Feske, Stefan. / Tissue resident and follicular Treg cell differentiation is regulated by CRAC channels. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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