Chronic alcohol consumption enhances iNKT cell maturation and activation

Hui Zhang; Faya Zhang; Zhaohui Zhu; Dung Luong; Gary G Meadows

doi:10.1016/j.taap.2014.11.013

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Chronic alcohol consumption enhances iNKT cell maturation and activation

Journal article

Open access

Peer reviewed

Chronic alcohol consumption enhances iNKT cell maturation and activation

Hui Zhang, Faya Zhang, Zhaohui Zhu, Dung Luong and Gary G Meadows

Toxicology and applied pharmacology, Vol.282(2), pp.139-150

01/15/2015

DOI: https://doi.org/10.1016/j.taap.2014.11.013

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https://hdl.handle.net/2376/105362

PMCID: PMC4299637

PMID: 25499027

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https://doi.org/10.1016/j.taap.2014.11.013View

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Abstract

Th1 Cells - drug effects

Cytokines - metabolism

Ethanol - toxicity

Mice, Inbred C57BL

NK Cell Lectin-Like Receptor Subfamily B - metabolism

Thymus Gland - cytology

Antigens, Differentiation, T-Lymphocyte - metabolism

Thymus Gland - drug effects

Th1 Cells - immunology

Antigens, CD - metabolism

Mice, Knockout

Lectins, C-Type - metabolism

Animals

Liver - drug effects

T-Lymphocytes - metabolism

Lymphocyte Activation - drug effects

T-Lymphocytes - drug effects

Antigens, Ly - metabolism

Liver - cytology

Mice

Interferon-gamma - genetics

Central Nervous System Depressants - toxicity

Interferon-gamma - biosynthesis

Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1(-) iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1(+)CD44(hi) mature iNKT cells but does not alter the number of NK1.1(-) immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1(-) iNKT cells, especially the NK1.1(-)CD44(lo) Stage I iNKT cells. The percentage of NKG2A(+) iNKT cells increases in all of the tissues and organs examined; whereas CXCR3(+) iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response.

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Title: Chronic alcohol consumption enhances iNKT cell maturation and activation
Creators: Hui Zhang - Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, USA. Electronic address: hzhang@wsu.edu
Faya Zhang - Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, USA
Zhaohui Zhu - Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, USA
Dung Luong - Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, USA
Gary G Meadows - Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, USA
Publication Details: Toxicology and applied pharmacology, Vol.282(2), pp.139-150
Academic Unit: Pharmaceutical Sciences, Department of
Publisher: United States
Grant note: K05 AA017149 / NIAAA NIH HHS K05AA017149 / NIAAA NIH HHS
Identifiers: 99900546753801842
Language: English
Resource Type: Journal article