Validation of RUNX1 as a potential target for treating circadian clock-induced obesity through preventing migration of group 3 innate lymphoid cells into intestine

Med Hypotheses. 2018 Apr:113:98-101. doi: 10.1016/j.mehy.2018.02.015. Epub 2018 Feb 19.

Abstract

The impact of unrhythmic circadian clock on obesity has started to be increasingly appreciated nowadays. Recently it was discovered that interaction between intestinal microbiota and unrhythmic circadian clock plays a key role in such a process. It involves relaying signals from microbiota through dendritic cells to group 3 innate lymphoid cells in the intestine and in the end impacting some of the key transcription factors of circadian clock. Breaking such a signal relay may prove to be an effective way reducing unrhythmic circadian clock-induced obesity. Here, we propose a hypothesis and design experiments to prove that suppressing one of the transcription factors, RUNX1, plays a key role in the homing of ILC3 cells to intestine. Such suppression is in response to a retinoic acid-RARα binding initiated pathway and results in the upregulation of gut-homing chemokine receptor CCR9 and downregulation of lymphoid tissue-homing receptor CCR7, which can then guide ILC3 cells to intestine. Therapies that can specifically sustain Runx1 expression in ILC3 cells may assist preventing the ever-escalating obesity problem in modern society.

MeSH terms

  • Animals
  • Cell Separation
  • Circadian Clocks
  • Circadian Rhythm
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Dendritic Cells / cytology
  • Flow Cytometry
  • Gastrointestinal Microbiome
  • Humans
  • Immunity, Innate
  • Intestinal Mucosa / metabolism
  • Lymphocytes / cytology*
  • Lymphoid Tissue / cytology
  • Mice
  • Obesity / complications*
  • Obesity / metabolism
  • Obesity / prevention & control
  • Tretinoin / metabolism

Substances

  • Core Binding Factor Alpha 2 Subunit
  • RUNX1 protein, human
  • Runx1 protein, mouse
  • Tretinoin