title: Chronic alcohol consumption enhances iNKT cell maturation and activation.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, USA. Electronic address: hzhang@wsu.edu.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, USA.
authors.forename: Faya
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, USA.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, USA.
authors.forename: Dung
authors.initials: D
authors.lastname: Luong
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210-1495, USA.
authors.forename: Gary G
authors.initials: GG
authors.lastname: Meadows
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D037181:Lectins, C-Type / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D002492:Central Nervous System Depressants; D016207:Cytokines; D000431:Ethanol; D007371:Interferon-gamma; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D000099192:CD69 Antigens; C527211:Klrb1c protein, mouse
keywords: Alcohol; Chemokines; NKT cells; Proliferation; Th1 response