1. Academic Validation
  2. Luteolin alleviates ulcerative colitis by restoring the balance of NCR-ILC3/NCR+ILC3 to repairing impaired intestinal barrier

Luteolin alleviates ulcerative colitis by restoring the balance of NCR-ILC3/NCR+ILC3 to repairing impaired intestinal barrier

  • Int Immunopharmacol. 2022 Nov;112:109251. doi: 10.1016/j.intimp.2022.109251.
Xueqian Xie 1 Meng Zhao 1 Shaowei Huang 1 Pengcheng Li 1 Peiqi Chen 1 Xia Luo 1 Qing Wang 1 Zengfeng Pan 1 Xiangling Li 2 Jinyan Chen 3 Bin Chen 4 Lian Zhou 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 2 Key Laboratory of Basic Research of Traditional Chinese Medicine, Guangxi University of Traditional Chinese Medicine, Nanning, China.
  • 3 Basic Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 4 First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China. Electronic address: [email protected].
  • 5 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: [email protected].
Abstract

Ulcerative colitis (UC) is a multifactorial, refractory chronic inflammatory disease. The primary factor leading to prolonged ulcerative colitis is the imbalance of the group 3 innate lymphoid cells (ILC3) subgroup resulting in the delayed reconstruction of damaged intestinal barrier. Previous studies show that luteolin had efficacy on UC, however, the potency of luteolin on restoring the balance of NCR-ILC3/NCR+ILC3 to repairing impaired intestinal barrier remains unclear. In this study, to investigate the potential mechanism of luteolin on ILC3 subgroup, we first evidenced that luteolin could promote transformation NCR-MNK3 to NCR+MNK3 in vitro. Then, a UC model was established in C57BL/6J mice to assess the efficacy of luteolin in restoring ILC3 subgroup balance and repairing intestinal barrier in chronic UC. Finally, the experiments in vitro validated the potential mechanism of luteolin in regulating ILC3 plasticity. The results showed that luteolin significantly alleviated the symptoms of DSS-induced UC in mice, including preventing body weight loss and decreasing the disease activity index (DAI) and intestinal damages. Additionally, luteolin increased NCR+ILC3 levels, promoted the production of IL-22 and decreased the levels of IL-17A and INF-γ in the intestine, and encourage intestinal barrier function recovery in UC mice by promoting the expression of ZO-1 and Occludin. Experiments in vitro revealed that luteolin facilitated the transformation of NCR-MNK3 to NCR+MNK3 and promoted the secretion of IL-22, which was linked to the Notch pathway. All results revealed that luteolin restored the balance of NCR-ILC3/NCR+ILC3 and contributed to repair of injured intestinal epithelium to alleviate ulcerative colitis.

Keywords

Intestinal barrier; Luteolin; NCR(+)ILC3; Notch pathway; Ulcerative colitis.

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