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2053 Long Noncoding RNA NEAT1 Regulates Acute Graft-Versus-Host Disease By Promoting Macrophage M1 Polarization through JNK Pathway

Program: Oral and Poster Abstracts
Session: 701. Experimental Transplantation: Basic and Translational: Poster I
Hematology Disease Topics & Pathways:
Research, Fundamental Science, GVHD, Diseases, Immune Disorders
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Ran Zhang, PhD1*, Zhenli Huang, PhD1*, Li Wang, MD1*, Weijie Cao, PhD1*, Donald Small, MD, PhD2, Ruiqi Zhu, PhD3*, Wei Shi, PhD3*, Zhongxing Jiang, MD4* and Linghui Xia3*

1Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
2Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
3Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
4The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China


Acute graft-versus-host disease (aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The function of macrophages in aGVHD is a hot point in current research. Long noncoding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) is closely related to immune-related diseases and affects the function of macrophages. However, the role of LncRNA NEAT1 in aGVHD is unclear in current study.


Peripheral blood mononuclear cells (PBMCs were collected from the patients with or without aGVHD after allo-HSCT. The expression of lncRNA NEAT1 in PBMCs was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic value of lncRNA NEAT1 in aGVHD was analyzed by receiver operating characteristic curve (ROC) and area under correlation curve (AUC). We transfected RAW264.7 cells and bone marrow-derived macrophages (BMDM) with NEAT1 lentiviral vector or NEAT1 small interfering RNA to change the expression level of NEAT1. The function of NEAT1 and its effect on JNK pathway were analyzed by flow cytometry, qRT-PCR, western blotting and ELISA. Finally, aGVHD mouse model was constructed to evaluate the function of JNK inhibitors in aGVHD.


Compared with non-aGVHD patients, LncRNA NEAT1 was significantly up-regulated in PBMCs of aGVHD patients. ROC and AUC analysis confirmed that the expression level of lncRNA NEAT1 was correlated with the occurrence of aGVHD, which may have certain diagnostic value in aGVHD. We found the expressions of NEAT1 in BMDM and RAW264.7 were remarkably increased after being stimulated with lipopolysaccharide (100ng/ml). The overexpression of lncRNA NEAT1 in RAW264.7 could significantly up-regulate the expression level of iNOS, and induce the differentiation into M1 type. Knockdown of lncRNA NEAT1 in BMDM could significantly down-regulate the gene expressions (iNOS and NLRP3), reduce the protein levels (iNOS, NLRP3 and p-JNK), decrease the proportion of M1 macrophages and inflammatory cytokines secretion (TNF-α and IL-1β), and inhibit the JNK pathway. We found that JNK inhibitor could perform the same function as knocking down lncRNA NEAT1 in BMDM. In addition, JNK inhibitor could improve the survival and pathology, decrease the inflammatory cytokines secretion (TNF-α and IL-1β), and reduce the infiltration of M1 macrophages into the target organs in aGVHD mouse model.


Our results showed that lncRNA NEAT1 may regulate the M1 polarization of macrophages and the secretion of inflammatory cytokines by regulating the JNK pathway. JNK inhibitor may reduce the inflammation in aGVHD mouse models by blocking the function of NEAT1 in macrophages. This study provides a promising therapeutic target for aGVHD.

Disclosures: Small: InSilico Medicine: Membership on an entity's Board of Directors or advisory committees; Pharos I&BT Co: Consultancy.

*signifies non-member of ASH