The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity

BackgroundThe incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide. Immune exhaustion has been reported in NTM-LD, but T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), a co-inhibitory receptor on T cells, has been scarcely studied.MethodsPatients...

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Autores principales:	Ping-Huai Wang, Ming-Fang Wu, Chi-Yu Hsu, Sheng-Wei Pan, Chin-Chung Shu, Shih-Lung Cheng
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	apoptosis cytokine Mycobacterium avium complex nontuberculous mycobacteria lung disease T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/e8e45c8f2dd1449597e6ac864c0a948b
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spelling	oai:doaj.org-article:e8e45c8f2dd1449597e6ac864c0a948b2021-11-11T12:16:58ZThe Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity1664-322410.3389/fimmu.2021.738056https://doaj.org/article/e8e45c8f2dd1449597e6ac864c0a948b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.738056/fullhttps://doaj.org/toc/1664-3224BackgroundThe incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide. Immune exhaustion has been reported in NTM-LD, but T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), a co-inhibitory receptor on T cells, has been scarcely studied.MethodsPatients with NTM-LD and healthy controls were prospectively recruited from July 2014 to August 2019 at three tertiary referral centers in Taiwan. We examined TIM3 expression on the T cells from the participants using flow cytometry. TIM3 expression was analyzed for different disease statuses and after treatment. The apoptosis and cytokine profiles were analyzed according to the TIM3 expression.ResultsAmong enrolled subjects (47 patients and 46 controls), TIM3 on CD4+ cells (6.44% vs. 4.12%, p = 0.028) and CD8+ cells (18.47% vs. 9.13%, p = 0.003) were higher in NTM-LD patients than in the controls. The TIM3 level on CD4+ and CD8+ T cells was positively associated with T-cell apoptosis in the NTM-LD patients. In stimulating peripheral blood mononuclear cells using PMA plus ionomycin, a high TIM3 level on T cells correlated with low interleukin-2 and tumor necrosis factor-alpha (TNF-α) on CD4+ cells and interferon-gamma and TNF-α on CD8+ T cells. For clinical manifestation, low body mass index (BMI), positive sputum acid-fast smear, and high radiographic score correlated with high TIM3 expression on T cells. After NTM treatment, TIM3+ decreased significantly on CD4+ and CD8+ T cells.ConclusionsIn patients with NTM-LD, TIM3+ expression increased over CD4+ and CD8+ T cells and correlated with cell apoptosis and specific cytokine attenuation. Clinically, TIM3+ T cells increased in patients with low BMI, high disease extent, and high bacilli burden but decreased after treatment.Ping-Huai WangMing-Fang WuMing-Fang WuChi-Yu HsuSheng-Wei PanSheng-Wei PanChin-Chung ShuChin-Chung ShuShih-Lung ChengShih-Lung ChengFrontiers Media S.A.articleapoptosiscytokineMycobacterium avium complexnontuberculous mycobacterialung diseaseT-cell immunoglobulin and mucin domain-containing protein 3 (TIM3)Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	apoptosis cytokine Mycobacterium avium complex nontuberculous mycobacteria lung disease T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) Immunologic diseases. Allergy RC581-607
spellingShingle	apoptosis cytokine Mycobacterium avium complex nontuberculous mycobacteria lung disease T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) Immunologic diseases. Allergy RC581-607 Ping-Huai Wang Ming-Fang Wu Ming-Fang Wu Chi-Yu Hsu Sheng-Wei Pan Sheng-Wei Pan Chin-Chung Shu Chin-Chung Shu Shih-Lung Cheng Shih-Lung Cheng The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity
description	BackgroundThe incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide. Immune exhaustion has been reported in NTM-LD, but T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), a co-inhibitory receptor on T cells, has been scarcely studied.MethodsPatients with NTM-LD and healthy controls were prospectively recruited from July 2014 to August 2019 at three tertiary referral centers in Taiwan. We examined TIM3 expression on the T cells from the participants using flow cytometry. TIM3 expression was analyzed for different disease statuses and after treatment. The apoptosis and cytokine profiles were analyzed according to the TIM3 expression.ResultsAmong enrolled subjects (47 patients and 46 controls), TIM3 on CD4+ cells (6.44% vs. 4.12%, p = 0.028) and CD8+ cells (18.47% vs. 9.13%, p = 0.003) were higher in NTM-LD patients than in the controls. The TIM3 level on CD4+ and CD8+ T cells was positively associated with T-cell apoptosis in the NTM-LD patients. In stimulating peripheral blood mononuclear cells using PMA plus ionomycin, a high TIM3 level on T cells correlated with low interleukin-2 and tumor necrosis factor-alpha (TNF-α) on CD4+ cells and interferon-gamma and TNF-α on CD8+ T cells. For clinical manifestation, low body mass index (BMI), positive sputum acid-fast smear, and high radiographic score correlated with high TIM3 expression on T cells. After NTM treatment, TIM3+ decreased significantly on CD4+ and CD8+ T cells.ConclusionsIn patients with NTM-LD, TIM3+ expression increased over CD4+ and CD8+ T cells and correlated with cell apoptosis and specific cytokine attenuation. Clinically, TIM3+ T cells increased in patients with low BMI, high disease extent, and high bacilli burden but decreased after treatment.
format	article
author	Ping-Huai Wang Ming-Fang Wu Ming-Fang Wu Chi-Yu Hsu Sheng-Wei Pan Sheng-Wei Pan Chin-Chung Shu Chin-Chung Shu Shih-Lung Cheng Shih-Lung Cheng
author_facet	Ping-Huai Wang Ming-Fang Wu Ming-Fang Wu Chi-Yu Hsu Sheng-Wei Pan Sheng-Wei Pan Chin-Chung Shu Chin-Chung Shu Shih-Lung Cheng Shih-Lung Cheng
author_sort	Ping-Huai Wang
title	The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity
title_short	The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity
title_full	The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity
title_fullStr	The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity
title_full_unstemmed	The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity
title_sort	trend of tim3 expression on t cells in patients with nontuberculous mycobacterial lung disease: from immune cell dysfunction to clinical severity
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e8e45c8f2dd1449597e6ac864c0a948b
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The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity

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