Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection thymocytes.

Autor: Ratiu JJ; Duke University, Department of Immunology, Durham, NC, 27710, USA. Jeremy.Ratiu@duke.edu., Barclay WE; Duke University, Department of Immunology, Durham, NC, 27710, USA., Lin E; Duke University, Department of Immunology, Durham, NC, 27710, USA., Wang Q; Duke University, Department of Immunology, Durham, NC, 27710, USA., Wellford S; Duke University, Department of Immunology, Durham, NC, 27710, USA., Mehta N; Duke University, Department of Immunology, Durham, NC, 27710, USA., Harnois MJ; Duke University, Department of Immunology, Durham, NC, 27710, USA., DiPalma D; Duke University, Department of Immunology, Durham, NC, 27710, USA., Roy S; Duke University, Department of Immunology, Durham, NC, 27710, USA., Contreras AV; Fox Chase Cancer Center, Blood Cell Development and Function Program, Philadelphia, PA, 19111, USA., Shinohara ML; Duke University, Department of Immunology, Durham, NC, 27710, USA.; Duke University, Department of Molecular Genetics and Microbiology, Durham, NC, 27710, USA., Wiest D; Fox Chase Cancer Center, Blood Cell Development and Function Program, Philadelphia, PA, 19111, USA., Zhuang Y; Duke University, Department of Immunology, Durham, NC, 27710, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Oct 06; Vol. 13 (1), pp. 5901. Date of Electronic Publication: 2022 Oct 06.
DOI: 10.1038/s41467-022-33610-4
Abstrakt: Production of a functional peripheral T cell compartment typically involves massive expansion of the bone marrow progenitors that seed the thymus. There are two main phases of expansion during T cell development, following T lineage commitment of double-negative (DN) 2 cells and after successful rearrangement and selection for functional TCRβ chains in DN3 thymocytes, which promotes the transition of DN4 cells to the DP stage. The signals driving the expansion of DN2 thymocytes are well studied. However, factors regulating the proliferation and survival of DN4 cells remain poorly understood. Here, we uncover an unexpected link between the transcription factor Zfp335 and control of cGAS/STING-dependent cell death in post-β-selection DN4 thymocytes. Zfp335 controls survival by sustaining expression of Ankle2, which suppresses cGAS/STING-dependent cell death. Together, this study identifies Zfp335 as a key transcription factor regulating the survival of proliferating post-β-selection thymocytes and demonstrates a key role for the cGAS/STING pathway in driving apoptosis of developing T cells.
(© 2022. The Author(s).)
Databáze: MEDLINE
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