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The circadian clock sets a spatial-temporal window for recent thymic emigrants.

Mili Minaduola1, Abudureyimujiang Aili2, Yuhui Bao1

  • 1Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology (Peking University), Peking University, Beijing, China.

Immunology and Cell Biology
|August 28, 2022
PubMed
Summary
This summary is machine-generated.

The circadian clock regulates T-cell egress from the thymus. Mature thymocytes show daily oscillations in number and emigration molecules, controlled by the BMAL1 clock gene.

Keywords:
BMAL1CCR2S1PR1circadian rhythmthymic egress

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Area of Science:

  • Immunology
  • Chronobiology
  • Cell Biology

Background:

  • The circadian clock influences immune cell functions in peripheral organs.
  • The impact of the circadian clock on T-cell development and egress from the thymus remains unclear.

Purpose of the Study:

  • To investigate the influence of the circadian clock on T-cell development and egress within the thymus.
  • To identify molecular mechanisms underlying circadian regulation of thymocyte egress.

Main Methods:

  • Flow cytometry was used to analyze thymocyte populations and subsets across different Zeitgeber times (ZT).
  • Expression levels of key molecules like S1PR1 and CCR2 were assessed.
  • The binding of the core clock molecule BMAL1 to gene promoters was examined.

Main Results:

  • CD4 and CD8 single-positive (SP) thymocytes, particularly mature subsets, displayed robust circadian oscillations.
  • Diurnal expression patterns of S1PR1 and CCR2, along with S1P and CCL2 gradients, correlated with rhythmic thymocyte egress.
  • Disruption of the light-dark cycle altered S1PR1 and CCR2 expression and thymocyte output.
  • The core clock molecule BMAL1 rhythmically bound to promoters of genes including Klf2, S1pr1, and Sphk2.

Conclusions:

  • Mature thymocyte egress from the thymus exhibits circadian dynamics, synchronized with T-cell homing to lymph nodes.
  • The core clock molecule BMAL1 likely drives thymocyte emigration via transcriptional regulation of relevant molecules.