Mannan-Binding Lectin Regulates Inflammatory Cytokine Production, Proliferation, and Cytotoxicity of Human Peripheral Natural Killer Cells

Natural killer (NK) cells represent the founding members of innate lymphoid cells (ILC) and play critical roles in inflammation and the immune response. NK cell effector functions are regulated and fine-tuned by various immune modulators. Mannan (or mannose)-binding lectin (MBL), a soluble C-type le...

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Main Authors: Jia Zhou, Mengyao Hu, Jie Li, Yan Liu, Jialiang Luo, Liyun Zhang, Xiao Lu, Daming Zuo, Zhengliang Chen
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2019/6738286
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author Jia Zhou
Mengyao Hu
Jie Li
Yan Liu
Jialiang Luo
Liyun Zhang
Xiao Lu
Daming Zuo
Zhengliang Chen
author_facet Jia Zhou
Mengyao Hu
Jie Li
Yan Liu
Jialiang Luo
Liyun Zhang
Xiao Lu
Daming Zuo
Zhengliang Chen
author_sort Jia Zhou
collection DOAJ
description Natural killer (NK) cells represent the founding members of innate lymphoid cells (ILC) and play critical roles in inflammation and the immune response. NK cell effector functions are regulated and fine-tuned by various immune modulators. Mannan (or mannose)-binding lectin (MBL), a soluble C-type lectin, is traditionally recognized as an initiator of the complement pathway. Recently, it is also considered as an immunomodulator by its interaction with kinds of immune cells. However, the effect of MBL on NK cell function remains unexplored. In this study, we found that human plasma MBL could interact directly with peripheral NK cells partially via its collagen-like region (CLR). This MBL binding markedly suppressed the interleukin-2- (IL-2-) induced inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) production but increased the IL-10 production in NK cells. In addition, the expression of activation surface markers such as CD25 and CD69 declined after MBL treatment. Also, MBL impaired the proliferation and lymphokine-activated killing (LAK) of NK cells. Moreover, we demonstrated that MBL inhibited IL-2-induced signal transducers and activators of transcription 5 (STAT5) activation in NK cells. In conclusion, we have uncovered a far unknown regulatory role of MBL on NK cells, a new clue that could be important in the immunomodulatory networks of immune responses.
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spelling doaj-art-db1333c405f64dc982abce03342a47712025-08-20T03:24:21ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/67382866738286Mannan-Binding Lectin Regulates Inflammatory Cytokine Production, Proliferation, and Cytotoxicity of Human Peripheral Natural Killer CellsJia Zhou0Mengyao Hu1Jie Li2Yan Liu3Jialiang Luo4Liyun Zhang5Xiao Lu6Daming Zuo7Zhengliang Chen8Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, ChinaThe Third Affiliate Hospital of Southern Medical University (Academy of Orthopedics Guangdong Province), Guangzhou, Guangdong 510000, ChinaDepartment of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, ChinaInstituteof Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, ChinaNatural killer (NK) cells represent the founding members of innate lymphoid cells (ILC) and play critical roles in inflammation and the immune response. NK cell effector functions are regulated and fine-tuned by various immune modulators. Mannan (or mannose)-binding lectin (MBL), a soluble C-type lectin, is traditionally recognized as an initiator of the complement pathway. Recently, it is also considered as an immunomodulator by its interaction with kinds of immune cells. However, the effect of MBL on NK cell function remains unexplored. In this study, we found that human plasma MBL could interact directly with peripheral NK cells partially via its collagen-like region (CLR). This MBL binding markedly suppressed the interleukin-2- (IL-2-) induced inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) production but increased the IL-10 production in NK cells. In addition, the expression of activation surface markers such as CD25 and CD69 declined after MBL treatment. Also, MBL impaired the proliferation and lymphokine-activated killing (LAK) of NK cells. Moreover, we demonstrated that MBL inhibited IL-2-induced signal transducers and activators of transcription 5 (STAT5) activation in NK cells. In conclusion, we have uncovered a far unknown regulatory role of MBL on NK cells, a new clue that could be important in the immunomodulatory networks of immune responses.http://dx.doi.org/10.1155/2019/6738286
spellingShingle Jia Zhou
Mengyao Hu
Jie Li
Yan Liu
Jialiang Luo
Liyun Zhang
Xiao Lu
Daming Zuo
Zhengliang Chen
Mannan-Binding Lectin Regulates Inflammatory Cytokine Production, Proliferation, and Cytotoxicity of Human Peripheral Natural Killer Cells
Mediators of Inflammation
title Mannan-Binding Lectin Regulates Inflammatory Cytokine Production, Proliferation, and Cytotoxicity of Human Peripheral Natural Killer Cells
title_full Mannan-Binding Lectin Regulates Inflammatory Cytokine Production, Proliferation, and Cytotoxicity of Human Peripheral Natural Killer Cells
title_fullStr Mannan-Binding Lectin Regulates Inflammatory Cytokine Production, Proliferation, and Cytotoxicity of Human Peripheral Natural Killer Cells
title_full_unstemmed Mannan-Binding Lectin Regulates Inflammatory Cytokine Production, Proliferation, and Cytotoxicity of Human Peripheral Natural Killer Cells
title_short Mannan-Binding Lectin Regulates Inflammatory Cytokine Production, Proliferation, and Cytotoxicity of Human Peripheral Natural Killer Cells
title_sort mannan binding lectin regulates inflammatory cytokine production proliferation and cytotoxicity of human peripheral natural killer cells
url http://dx.doi.org/10.1155/2019/6738286
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