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STAT1 maintains naive CD8+ T cell quiescence by suppressing the type I IFN-STAT4-mTORC1 signaling axis.


ABSTRACT: Naïve CD8+ T cell quiescence is maintained at a steady state. Although this state of quiescence involves various cell-intrinsic and cell-extrinsic regulators, the mechanisms underlying this regulation remain incompletely understood. Here, we found that signal transducer and activator of transcription 1 (STAT1), a key transcription factor downstream of interferon receptor (IFNR) signaling, plays a cell-intrinsic role in maintaining naïve CD8+ T cell quiescence. STAT1-deficient mice showed enhanced proliferation of peripheral naïve CD8+ T cells, which resulted in an abnormal increase in the number of CD44hi memory/activated phenotype cells and an enlargement of secondary lymphoid tissues. This phenomenon was not observed in IFNR-deficient mice but was paradoxically dependent on type I interferon and its alternative signaling pathway via the STAT4–RagD–lysosomal mTORC1 axis. Collectively, these findings underline the importance of STAT1 in regulating the homeostasis of peripheral naïve CD8+ T cells by suppressing their responsiveness to homeostatic cues at a steady state.

SUBMITTER: Kye YC 

PROVIDER: S-EPMC8442933 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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STAT1 maintains naïve CD8<sup>+</sup> T cell quiescence by suppressing the type I IFN-STAT4-mTORC1 signaling axis.

Kye Yoon-Chul YC   Lee Gil-Woo GW   Lee Sung-Woo SW   Ju Young-Jun YJ   Kim Hee-Ok HO   Yun Cheol-Heui CH   Cho Jae-Ho JH  

Science advances 20210901 36


Naïve CD8<sup>+</sup> T cell quiescence is maintained at a steady state. Although this state of quiescence involves various cell-intrinsic and cell-extrinsic regulators, the mechanisms underlying this regulation remain incompletely understood. Here, we found that signal transducer and activator of transcription 1 (STAT1), a key transcription factor downstream of interferon receptor (IFNR) signaling, plays a cell-intrinsic role in maintaining naïve CD8<sup>+</sup> T cell quiescence. STAT1-deficie  ...[more]

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