Cytotoxic Function and Cytokine Production of Natural Killer Cells and Natural Killer T-Like Cells in Systemic Lupus Erythematosis Regulation with Interleukin-15

Natural killer cells and NKT-like cells are the first line immune defense against tumor and virus infection. Deficient NK and NKT-like cell effector function may contribute to increased susceptibility to infection in SLE patients. We sought to examine the perforin and granzyme B expression, interfer...

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Main Authors: Syh-Jae Lin, Ming-Ling Kuo, Hsiu-Shan Hsiao, Pei-Tzu Lee, Wen-I Lee, Ji-Yih Chen, Jing-Long Huang
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2019/4236562
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author Syh-Jae Lin
Ming-Ling Kuo
Hsiu-Shan Hsiao
Pei-Tzu Lee
Wen-I Lee
Ji-Yih Chen
Jing-Long Huang
author_facet Syh-Jae Lin
Ming-Ling Kuo
Hsiu-Shan Hsiao
Pei-Tzu Lee
Wen-I Lee
Ji-Yih Chen
Jing-Long Huang
author_sort Syh-Jae Lin
collection DOAJ
description Natural killer cells and NKT-like cells are the first line immune defense against tumor and virus infection. Deficient NK and NKT-like cell effector function may contribute to increased susceptibility to infection in SLE patients. We sought to examine the perforin and granzyme B expression, interferon-gamma (IFN-γ), and tumor-necrosis factor-alpha (TNF-α) production and CD107a degranulation of NK and NKT-like cells from SLE patients and their regulation by IL-15. We established that (1) perforin expression on SLE NK cells was decreased but unrelated to disease activity; (2) the MFI of granzyme B was increased in NK cells from SLE patients with active disease, associated with increased percentages of granzyme B+ CD56bright NK cells; (3) NK cells from active SLE patients, both CD56dim and CD56bright NK subsets, produced higher IFN-γ compared to controls; (4) CD56dim, but not CD56bright NK cells from active SLE patients, produced lower TNF-α, compared to inactive SLE patients and controls; (5) CD107a degranulation of SLE NK cells was comparable to controls; (6) IL-15 enhanced perforin/granzyme B expression, IFN-γ/TNF-α production, and CD107a degranulation of NK cells from SLE patients; and (7) similar observations were found for CD56+CD3+ NKT-like cells. Taken together, we demonstrated the differential expression of the heightened granzyme B and decreased TNF-α in NK and NKT-like cells in SLE patients. Higher granzyme B expression of NK and NKT-like cells in active SLE patients, further enhanced by circulating IL-15, may contribute to the maintenance of inflammation in SLE.
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spelling doaj-art-b6620691ee4440908663b9499e422f952025-02-03T01:27:27ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/42365624236562Cytotoxic Function and Cytokine Production of Natural Killer Cells and Natural Killer T-Like Cells in Systemic Lupus Erythematosis Regulation with Interleukin-15Syh-Jae Lin0Ming-Ling Kuo1Hsiu-Shan Hsiao2Pei-Tzu Lee3Wen-I Lee4Ji-Yih Chen5Jing-Long Huang6Department of Pediatrics, Division of Asthma, Allergy, and Rheumatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, TaiwanDepartment of Pediatrics, Division of Asthma, Allergy, and Rheumatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, TaiwanDepartment of Pediatrics, Division of Asthma, Allergy, and Rheumatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, TaiwanDepartment of Pediatrics, Division of Asthma, Allergy, and Rheumatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, TaiwanDepartment of Pediatrics, Division of Asthma, Allergy, and Rheumatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, TaiwanDepartment of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Tao-Yuan, TaiwanDepartment of Pediatrics, Division of Asthma, Allergy, and Rheumatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, TaiwanNatural killer cells and NKT-like cells are the first line immune defense against tumor and virus infection. Deficient NK and NKT-like cell effector function may contribute to increased susceptibility to infection in SLE patients. We sought to examine the perforin and granzyme B expression, interferon-gamma (IFN-γ), and tumor-necrosis factor-alpha (TNF-α) production and CD107a degranulation of NK and NKT-like cells from SLE patients and their regulation by IL-15. We established that (1) perforin expression on SLE NK cells was decreased but unrelated to disease activity; (2) the MFI of granzyme B was increased in NK cells from SLE patients with active disease, associated with increased percentages of granzyme B+ CD56bright NK cells; (3) NK cells from active SLE patients, both CD56dim and CD56bright NK subsets, produced higher IFN-γ compared to controls; (4) CD56dim, but not CD56bright NK cells from active SLE patients, produced lower TNF-α, compared to inactive SLE patients and controls; (5) CD107a degranulation of SLE NK cells was comparable to controls; (6) IL-15 enhanced perforin/granzyme B expression, IFN-γ/TNF-α production, and CD107a degranulation of NK cells from SLE patients; and (7) similar observations were found for CD56+CD3+ NKT-like cells. Taken together, we demonstrated the differential expression of the heightened granzyme B and decreased TNF-α in NK and NKT-like cells in SLE patients. Higher granzyme B expression of NK and NKT-like cells in active SLE patients, further enhanced by circulating IL-15, may contribute to the maintenance of inflammation in SLE.http://dx.doi.org/10.1155/2019/4236562
spellingShingle Syh-Jae Lin
Ming-Ling Kuo
Hsiu-Shan Hsiao
Pei-Tzu Lee
Wen-I Lee
Ji-Yih Chen
Jing-Long Huang
Cytotoxic Function and Cytokine Production of Natural Killer Cells and Natural Killer T-Like Cells in Systemic Lupus Erythematosis Regulation with Interleukin-15
Mediators of Inflammation
title Cytotoxic Function and Cytokine Production of Natural Killer Cells and Natural Killer T-Like Cells in Systemic Lupus Erythematosis Regulation with Interleukin-15
title_full Cytotoxic Function and Cytokine Production of Natural Killer Cells and Natural Killer T-Like Cells in Systemic Lupus Erythematosis Regulation with Interleukin-15
title_fullStr Cytotoxic Function and Cytokine Production of Natural Killer Cells and Natural Killer T-Like Cells in Systemic Lupus Erythematosis Regulation with Interleukin-15
title_full_unstemmed Cytotoxic Function and Cytokine Production of Natural Killer Cells and Natural Killer T-Like Cells in Systemic Lupus Erythematosis Regulation with Interleukin-15
title_short Cytotoxic Function and Cytokine Production of Natural Killer Cells and Natural Killer T-Like Cells in Systemic Lupus Erythematosis Regulation with Interleukin-15
title_sort cytotoxic function and cytokine production of natural killer cells and natural killer t like cells in systemic lupus erythematosis regulation with interleukin 15
url http://dx.doi.org/10.1155/2019/4236562
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