Chronic alcohol consumption inhibits peripheral NK cell development and maturation by decreasing the availability of IL-15

Faya Zhang; Alex Little; Hui Zhang

doi:10.1189/jlb.1A0716-298RR

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Chronic alcohol consumption inhibits peripheral NK cell development and maturation by decreasing the availability of IL-15

Journal article

Open access

Peer reviewed

Chronic alcohol consumption inhibits peripheral NK cell development and maturation by decreasing the availability of IL-15

Faya Zhang, Alex Little and Hui Zhang

Journal of leukocyte biology, Vol.101(4), pp.1015-1027

04/2017

DOI: https://doi.org/10.1189/jlb.1A0716-298RR

Handle:

https://hdl.handle.net/2376/113066

PMCID: PMC5346179

PMID: 27837016

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https://doi.org/10.1189/jlb.1A0716-298RRView

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Abstract

NK Cell Lectin-Like Receptor Subfamily A - metabolism

Cell Proliferation

Cell Count

Granzymes - metabolism

Mice, Inbred C57BL

Interleukin-15 Receptor alpha Subunit - metabolism

T-Box Domain Proteins - metabolism

Alcohol Drinking - immunology

Killer Cells, Natural - cytology

Animals

Spleen - metabolism

Bone Marrow - metabolism

Interleukin-15 - metabolism

Killer Cells, Natural - immunology

Female

Cell Differentiation

Chronic Disease

Receptors, Immunologic - metabolism

NK cells are innate immune cells and have important roles in antiviral and antitumor immunity. Based on the transcriptional regulation, organ distribution, and cell function, NK cells have recently been further divided into cytotoxic conventional NK cells (cNK) and noncytotoxic helper-like group 1 innate lymphoid cells (ILC1s). It is well known that chronic alcohol consumption decreases peripheral NK cell number and cytolytic activity; however, the underlying mechanism remains to be elucidated. How chronic alcohol consumption affects ILC1s is, to our knowledge, completely unexplored. Herein, we used a well-established mouse model of chronic alcohol consumption to study the effects of alcohol on transcription factor expression, maturation, and cytokine production of cNK cells and ILC1s in various organs. We found that alcohol consumption significantly decreased Eomes-expressing cNK cells in all the examined organs, except BM, but did not significantly affect ILC1s. Alcohol consumption compromised cNK cell development and maturation. Exogenous IL-15/IL-15Rα treatment caused full recovery of Eomes-expressing cNK cell number and maturation. Taken together, our data indicated that chronic alcohol consumption decreases cNK cell number and cytolytic activity by arresting cNK cell development at the CD27 CD11b stage. This developmental arrest of NK cells results from a lack of IL-15 availability in the microenvironment. IL-15/IL-15Rα treatment can recover alcohol consumption-induced developmental defect in NK cells.

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Title: Chronic alcohol consumption inhibits peripheral NK cell development and maturation by decreasing the availability of IL-15
Creators: Faya Zhang - Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington, USA
Alex Little - Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington, USA
Hui Zhang - Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington, USA hzhang@wsu.edu
Publication Details: Journal of leukocyte biology, Vol.101(4), pp.1015-1027
Academic Unit: Pharmaceutical Sciences, Department of
Publisher: United States
Grant note: R21 AA022098 / NIAAA NIH HHS
Identifiers: 99900548388401842
Language: English
Resource Type: Journal article