Melatonin-induced lncRNA LINC01512 prevents Treg/Th17 imbalance by promoting SIRT1 expression in necrotizing enterocolitis

Xiaoyan Gao; Wangkai Liu; Pingmin Gao; Sitao Li; Zhaoyu Chen; Fei Ma

doi:10.1016/j.intimp.2021.107787

Melatonin-induced lncRNA LINC01512 prevents Treg/Th17 imbalance by promoting SIRT1 expression in necrotizing enterocolitis

Int Immunopharmacol. 2021 Jul:96:107787. doi: 10.1016/j.intimp.2021.107787. Epub 2021 May 24.

Authors

Xiaoyan Gao¹, Wangkai Liu², Pingmin Gao¹, Sitao Li³, Zhaoyu Chen¹, Fei Ma⁴

Affiliations

¹ Department of Neonatology, The Foshan Women and Children Hospital Affiliated to Southern Medical University, Foshan, China.
² Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
³ Department of Pediatrics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁴ Department of Pediatrics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: mafei7@mail.sysu.edu.cn.

PMID: 34162151
DOI: 10.1016/j.intimp.2021.107787

Abstract

Despite the fact that melatonin regulates the expression of long noncoding RNAs (lncRNAs) under different physiological and pathological conditions, it has not been confirmed whether melatonin-induced lncRNAs regulate the differentiation of Treg and Th17 cells. Herein, we show that the expression of LINC01512 is significantly down-regulated and correlates with imbalanced Treg/Th17 ratios in necrotising enterocolitis (NEC) tissues. Through gain- and loss-of-function approaches, we found that LINC01512 promotes the differentiation of Treg cells but interferes with that of Th17 cells. Mechanistically, LINC01512 promotes SIRT1 in Treg and Th17 cells, and subsequently enhances the differentiation of Treg cells and inhibits that of Th17 cells. Furthermore, we demonstrate that melatonin up-regulates the transcription of LINC01512 via the AMPK signalling pathway and that the blockade of AMPK represses LINC01512 expression in Treg and Th17 cells. Overall, our results confirm that SIRT1-regulated differentiation of Treg/Th17 cells is actually modulated by melatonin-induced LINC0512. Moreover, manipulation of the AMPK/LINC01512/SIRT1 axis via melatonin may be a novel therapeutic approach to reduce inflammation.

Keywords: Melatonin; Necrotizing enterocolitis; Th17 cells; Treg cells; lncRNA.

MeSH terms

Cell Differentiation
Enterocolitis, Necrotizing / immunology*
Humans
Melatonin / pharmacology*
RNA, Long Noncoding*
Sirtuin 1 / immunology*
T-Lymphocytes, Regulatory / drug effects*
T-Lymphocytes, Regulatory / immunology
Th17 Cells / drug effects*
Th17 Cells / immunology

Substances

RNA, Long Noncoding
SIRT1 protein, human
Sirtuin 1
Melatonin