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LILRA3 is increased in IBD patients and functions as an anti-inflammatory modulator
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  • Xiucai LanOrcid,
  • Fenghua Liu,
  • Ying Chang,
  • Jing Liu,
  • Xiuhua Lan,
  • Li Xiang,
  • Feng Zhou,
  • Qiu Zhao
Xiucai Lan
Orcid
Zhongshan Hospital Fudan University
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Fenghua Liu
Shanghai Xuhui Central Hospital
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Ying Chang
Wuhan University Zhongnan Hospital
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Jing Liu
Wuhan University Zhongnan Hospital
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Xiuhua Lan
Shanghai Institute of Materia Medica CAS
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Li Xiang
Wuhan University Zhongnan Hospital
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Feng Zhou
Wuhan University Zhongnan Hospital
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Qiu Zhao
Wuhan University Zhongnan Hospital
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Peer review status:IN REVISION

13 Apr 2020Submitted to Clinical & Experimental Immunology
14 Apr 2020Assigned to Editor
14 Apr 2020Submission Checks Completed
17 Apr 2020Reviewer(s) Assigned
02 May 2020Review(s) Completed, Editorial Evaluation Pending
03 May 2020Editorial Decision: Revise Major

Abstract

Growing evidence shows that a homozygous 6.7-kb deletion of the novel anti-inflammatory molecule leukocyte immunoglobulin like receptor A3 (LILRA3) is associated with many autoimmune disorders. However, its effects on pathogenesis of inflammatory bowel disease (IBD) have not been clarified yet. LILRA3 is mainly expressed in monocytes, whereas its effects on biological behaviors of monocytes have not been systematically reported. To investigate the association between LILRA3 polymorphism and IBD susceptibility, LILRA3 polymorphism was assessed in 378 IBD patients and 509 healthy controls in our study, quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry (IHC) were employed to detect the LILRA3 expression in IBD patient blood and intestinal samples. Despite no association of the polymorphism with IBD development was found, LILRA3 expression was markedly increased in IBD patients compared with healthy controls. Human U937 monocyte cell line was employed to establish LILRA3-overexpressing cells and the effects of LILRA3 on the biological behaviors of U937 cells were systematically explored. We found that overexpression of LILRA3 in monocytes led to significant decreases in secretion of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). Additionally, LILRA3 abated monocyte migration by reducing the expression of several chemokines and enhanced monocyte phagocytosis by increasing CD36 expression. Furthermore, LILRA3 promoted monocyte proliferation through a combination of Akt and MEK/Erk signaling pathways. We report for the first time that LILRA3 is related to IBD and functions as an anti-inflammatory modulator in U937 cells.