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

First Author  Ratiu JJ Year  2022
Journal  Nat Commun Volume  13
Issue  1 Pages  5901
PubMed ID  36202870 Mgi Jnum  J:334079
Mgi Id  MGI:7344942 Doi  10.1038/s41467-022-33610-4
Citation  Ratiu JJ, et al. (2022) Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-beta selection thymocytes. Nat Commun 13(1):5901
abstractText  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 TCRbeta 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-beta-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-beta-selection thymocytes and demonstrates a key role for the cGAS/STING pathway in driving apoptosis of developing T cells.
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