Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice

Karsten Buschard; Axel Jacob Kornerup Hansen; Karen Jensen; Dicky J. Lindenbergh-Kortleve; Lillian F. de Ruiter; Thomas Cæcius Krohn; Majbritt Ravn Hufeldt; Finn Kvist Vogensen; Bent Aasted; Thomas Osterbye; Bart O. Roep; Colin de Haar; Edward E. Nieuwenhuis

doi:10.1371/journal.pone.0017931

Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice

Karsten Buschard, Axel Jacob Kornerup Hansen, Karen Jensen, Dicky J. Lindenbergh-Kortleve, Lillian F. de Ruiter, Thomas Cæcius Krohn, Majbritt Ravn Hufeldt, Finn Kvist Vogensen, Bent Aasted, Thomas Osterbye, Bart O. Roep, Colin de Haar, Edward E. Nieuwenhuis

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Abstract

Background: Ethanol ('alcohol') is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules. Methods: The study included cellular in vitro tests using α-galactosylceramide (αGalCer), and in vivo NOD mice experiments detecting diabetes incidence and performing behavioural and bacterial analyses. Results: Alcohol in concentrations from 0.6% to 2.5% increased IL-2 production from NKT cells stimulated with αGalCer by 60% (p<0.05). CD1d expressed on HeLa cells contained significantly increasing amounts of αGalCer with increasing concentrations of alcohol, suggesting that alcohol facilitated the passive loading of αGalCer to CD1d. NOD mice were found to tolerate 5% ethanol in their drinking water without signs of impairment in liver function. Giving this treatment, the diabetes incidence declined significantly. Higher numbers of CD3+CD49b+ NKT cells were found in spleen and liver of the alcohol treated compared to the control mice (p<0.05), whereas the amount of CD4+Foxp3+ regulator T cells did not differ. Increased concentrations of IFN-γ were detected in 24-hour blood samples of alcohol treated mice. Behavioural studies showed no change in attitude of the ethanol-consuming mice, and bacterial composition of caecum samples was not affected by alcohol, disqualifying these as protective mechanisms. Conclusion: Alcohol facilitates the uptake of glycolipids and the stimulation of NKT cells, which are known to counteract Type 1 diabetes development. We propose that this is the acting mechanism by which treatment with alcohol reduces the incidence of diabetes in NOD mice. This is corroborated by epidemiology showing beneficial effect of alcohol to reduce the severity of atherosclerosis and related diseases.

Original language	English
Journal	P L o S One
Volume	6
Issue number	4
Number of pages	7
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0017931
Publication status	Published - 2011

Keywords

Former LIFE faculty

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Buschard, K., Hansen, A. J. K., Jensen, K., Lindenbergh-Kortleve, D. J., de Ruiter, L. F., Krohn, T. C., Hufeldt, M. R., Vogensen, F. K., Aasted, B., Osterbye, T., Roep, B. O., de Haar, C., & Nieuwenhuis, E. E. (2011). Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice. P L o S One, 6(4). https://doi.org/10.1371/journal.pone.0017931

Buschard, K, Hansen, AJK, Jensen, K, Lindenbergh-Kortleve, DJ, de Ruiter, LF, Krohn, TC, Hufeldt, MR, Vogensen, FK, Aasted, B, Osterbye, T, Roep, BO, de Haar, C & Nieuwenhuis, EE 2011, 'Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice', P L o S One, vol. 6, no. 4. https://doi.org/10.1371/journal.pone.0017931

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title = "Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice",

abstract = "Background: Ethanol ('alcohol') is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules. Methods: The study included cellular in vitro tests using α-galactosylceramide (αGalCer), and in vivo NOD mice experiments detecting diabetes incidence and performing behavioural and bacterial analyses. Results: Alcohol in concentrations from 0.6% to 2.5% increased IL-2 production from NKT cells stimulated with αGalCer by 60% (p<0.05). CD1d expressed on HeLa cells contained significantly increasing amounts of αGalCer with increasing concentrations of alcohol, suggesting that alcohol facilitated the passive loading of αGalCer to CD1d. NOD mice were found to tolerate 5% ethanol in their drinking water without signs of impairment in liver function. Giving this treatment, the diabetes incidence declined significantly. Higher numbers of CD3+CD49b+ NKT cells were found in spleen and liver of the alcohol treated compared to the control mice (p<0.05), whereas the amount of CD4+Foxp3+ regulator T cells did not differ. Increased concentrations of IFN-γ were detected in 24-hour blood samples of alcohol treated mice. Behavioural studies showed no change in attitude of the ethanol-consuming mice, and bacterial composition of caecum samples was not affected by alcohol, disqualifying these as protective mechanisms. Conclusion: Alcohol facilitates the uptake of glycolipids and the stimulation of NKT cells, which are known to counteract Type 1 diabetes development. We propose that this is the acting mechanism by which treatment with alcohol reduces the incidence of diabetes in NOD mice. This is corroborated by epidemiology showing beneficial effect of alcohol to reduce the severity of atherosclerosis and related diseases.",

keywords = "Former LIFE faculty, Type 1 diabetes, Alkohol, NOD mus, CD1d",

author = "Karsten Buschard and Hansen, {Axel Jacob Kornerup} and Karen Jensen and Lindenbergh-Kortleve, {Dicky J.} and {de Ruiter}, {Lillian F.} and Krohn, {Thomas C{\ae}cius} and Hufeldt, {Majbritt Ravn} and Vogensen, {Finn Kvist} and Bent Aasted and Thomas Osterbye and Roep, {Bart O.} and {de Haar}, Colin and Nieuwenhuis, {Edward E.}",

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T1 - Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice

AU - Buschard, Karsten

AU - Hansen, Axel Jacob Kornerup

AU - Jensen, Karen

AU - Lindenbergh-Kortleve, Dicky J.

AU - de Ruiter, Lillian F.

AU - Krohn, Thomas Cæcius

AU - Hufeldt, Majbritt Ravn

AU - Vogensen, Finn Kvist

AU - Aasted, Bent

AU - Osterbye, Thomas

AU - Roep, Bart O.

AU - de Haar, Colin

AU - Nieuwenhuis, Edward E.

N1 - e17931

PY - 2011

Y1 - 2011

N2 - Background: Ethanol ('alcohol') is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules. Methods: The study included cellular in vitro tests using α-galactosylceramide (αGalCer), and in vivo NOD mice experiments detecting diabetes incidence and performing behavioural and bacterial analyses. Results: Alcohol in concentrations from 0.6% to 2.5% increased IL-2 production from NKT cells stimulated with αGalCer by 60% (p<0.05). CD1d expressed on HeLa cells contained significantly increasing amounts of αGalCer with increasing concentrations of alcohol, suggesting that alcohol facilitated the passive loading of αGalCer to CD1d. NOD mice were found to tolerate 5% ethanol in their drinking water without signs of impairment in liver function. Giving this treatment, the diabetes incidence declined significantly. Higher numbers of CD3+CD49b+ NKT cells were found in spleen and liver of the alcohol treated compared to the control mice (p<0.05), whereas the amount of CD4+Foxp3+ regulator T cells did not differ. Increased concentrations of IFN-γ were detected in 24-hour blood samples of alcohol treated mice. Behavioural studies showed no change in attitude of the ethanol-consuming mice, and bacterial composition of caecum samples was not affected by alcohol, disqualifying these as protective mechanisms. Conclusion: Alcohol facilitates the uptake of glycolipids and the stimulation of NKT cells, which are known to counteract Type 1 diabetes development. We propose that this is the acting mechanism by which treatment with alcohol reduces the incidence of diabetes in NOD mice. This is corroborated by epidemiology showing beneficial effect of alcohol to reduce the severity of atherosclerosis and related diseases.

AB - Background: Ethanol ('alcohol') is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules. Methods: The study included cellular in vitro tests using α-galactosylceramide (αGalCer), and in vivo NOD mice experiments detecting diabetes incidence and performing behavioural and bacterial analyses. Results: Alcohol in concentrations from 0.6% to 2.5% increased IL-2 production from NKT cells stimulated with αGalCer by 60% (p<0.05). CD1d expressed on HeLa cells contained significantly increasing amounts of αGalCer with increasing concentrations of alcohol, suggesting that alcohol facilitated the passive loading of αGalCer to CD1d. NOD mice were found to tolerate 5% ethanol in their drinking water without signs of impairment in liver function. Giving this treatment, the diabetes incidence declined significantly. Higher numbers of CD3+CD49b+ NKT cells were found in spleen and liver of the alcohol treated compared to the control mice (p<0.05), whereas the amount of CD4+Foxp3+ regulator T cells did not differ. Increased concentrations of IFN-γ were detected in 24-hour blood samples of alcohol treated mice. Behavioural studies showed no change in attitude of the ethanol-consuming mice, and bacterial composition of caecum samples was not affected by alcohol, disqualifying these as protective mechanisms. Conclusion: Alcohol facilitates the uptake of glycolipids and the stimulation of NKT cells, which are known to counteract Type 1 diabetes development. We propose that this is the acting mechanism by which treatment with alcohol reduces the incidence of diabetes in NOD mice. This is corroborated by epidemiology showing beneficial effect of alcohol to reduce the severity of atherosclerosis and related diseases.

KW - Former LIFE faculty

KW - Type 1 diabetes

KW - Alkohol

KW - NOD mus

KW - CD1d

U2 - 10.1371/journal.pone.0017931

DO - 10.1371/journal.pone.0017931

M3 - Journal article

C2 - 21483778

SN - 1932-6203

VL - 6

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 4

ER -

Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice

Abstract

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