Peripheral immune circadian variation, synchronisation and possible dysrhythmia in established type 1 diabetes

Craig A Beam; Eleni Beli; Clive H Wasserfall; Stephanie E Woerner; Megan T Legge; Carmella Evans-Molina; Kieran M McGrail; Ryan Silk; Maria B Grant; Mark A Atkinson; Linda A DiMeglio

doi:10.1007/s00125-021-05468-6

Peripheral immune circadian variation, synchronisation and possible dysrhythmia in established type 1 diabetes

Craig A Beam, Eleni Beli, Clive H Wasserfall, Stephanie E Woerner, Megan T Legge, Carmella Evans-Molina, Kieran M McGrail, Ryan Silk, Maria B Grant, Mark A Atkinson, Linda A DiMeglio

Wellcome Wolfson Institute for Experimental Medicine

Research output: Contribution to journal › Article › peer-review

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Abstract

AIMS/HYPOTHESIS: The circadian clock influences both diabetes and immunity. Our goal in this study was to characterise more thoroughly the circadian patterns of immune cell populations and cytokines that are particularly relevant to the immune pathology of type 1 diabetes and thus fill in a current gap in our understanding of this disease.

METHODS: Ten individuals with established type 1 diabetes (mean disease duration 11 years, age 18-40 years, six female) participated in a circadian sampling protocol, each providing six blood samples over a 24 h period.

RESULTS: Daily ranges of population frequencies were sometimes large and possibly clinically significant. Several immune populations, such as dendritic cells, CD4 and CD8 T cells and their effector memory subpopulations, CD4 regulatory T cells, B cells and cytokine IL-6, exhibited statistically significant circadian rhythmicity. In a comparison with historical healthy control individuals, but using shipped samples, we observed that participants with type 1 diabetes had statistically significant phase shifts occurring in the time of peak occurrence of B cells (+4.8 h), CD4 and CD8 T cells (~ +5 h) and their naive and effector memory subsets (~ +3.3 to +4.5 h), and regulatory T cells (+4.1 h). An independent streptozotocin murine experiment confirmed the phase shifting of CD8 T cells and suggests that circadian dysrhythmia in type 1 diabetes might be an effect and not a cause of the disease.

CONCLUSIONS/INTERPRETATION: Future efforts investigating this newly described aspect of type 1 diabetes in human participants are warranted. Peripheral immune populations should be measured near the same time of day in order to reduce circadian-related variation.

Original language	English
Journal	Diabetologia
Early online date	18 May 2021
DOIs	https://doi.org/10.1007/s00125-021-05468-6
Publication status	Early online date - 18 May 2021

Keywords

circadian ryhtms
type 1 diabetes

UN SDGs

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

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Peripheral immune circadian variation, synchronisation and possible dysrhythmia in established type 1 diabetes
Copyright 2021 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 1.19 MBLicence: CC BY

Cite this

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title = "Peripheral immune circadian variation, synchronisation and possible dysrhythmia in established type 1 diabetes",

abstract = "AIMS/HYPOTHESIS: The circadian clock influences both diabetes and immunity. Our goal in this study was to characterise more thoroughly the circadian patterns of immune cell populations and cytokines that are particularly relevant to the immune pathology of type 1 diabetes and thus fill in a current gap in our understanding of this disease.METHODS: Ten individuals with established type 1 diabetes (mean disease duration 11 years, age 18-40 years, six female) participated in a circadian sampling protocol, each providing six blood samples over a 24 h period.RESULTS: Daily ranges of population frequencies were sometimes large and possibly clinically significant. Several immune populations, such as dendritic cells, CD4 and CD8 T cells and their effector memory subpopulations, CD4 regulatory T cells, B cells and cytokine IL-6, exhibited statistically significant circadian rhythmicity. In a comparison with historical healthy control individuals, but using shipped samples, we observed that participants with type 1 diabetes had statistically significant phase shifts occurring in the time of peak occurrence of B cells (+4.8 h), CD4 and CD8 T cells (~ +5 h) and their naive and effector memory subsets (~ +3.3 to +4.5 h), and regulatory T cells (+4.1 h). An independent streptozotocin murine experiment confirmed the phase shifting of CD8 T cells and suggests that circadian dysrhythmia in type 1 diabetes might be an effect and not a cause of the disease.CONCLUSIONS/INTERPRETATION: Future efforts investigating this newly described aspect of type 1 diabetes in human participants are warranted. Peripheral immune populations should be measured near the same time of day in order to reduce circadian-related variation.",

keywords = "circadian ryhtms, type 1 diabetes",

author = "Beam, {Craig A} and Eleni Beli and Wasserfall, {Clive H} and Woerner, {Stephanie E} and Legge, {Megan T} and Carmella Evans-Molina and McGrail, {Kieran M} and Ryan Silk and Grant, {Maria B} and Atkinson, {Mark A} and DiMeglio, {Linda A}",

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doi = "10.1007/s00125-021-05468-6",

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AU - Beam, Craig A

AU - Beli, Eleni

AU - Wasserfall, Clive H

AU - Woerner, Stephanie E

AU - Legge, Megan T

AU - Evans-Molina, Carmella

AU - McGrail, Kieran M

AU - Silk, Ryan

AU - Grant, Maria B

AU - Atkinson, Mark A

AU - DiMeglio, Linda A

PY - 2021/5/18

Y1 - 2021/5/18

N2 - AIMS/HYPOTHESIS: The circadian clock influences both diabetes and immunity. Our goal in this study was to characterise more thoroughly the circadian patterns of immune cell populations and cytokines that are particularly relevant to the immune pathology of type 1 diabetes and thus fill in a current gap in our understanding of this disease.METHODS: Ten individuals with established type 1 diabetes (mean disease duration 11 years, age 18-40 years, six female) participated in a circadian sampling protocol, each providing six blood samples over a 24 h period.RESULTS: Daily ranges of population frequencies were sometimes large and possibly clinically significant. Several immune populations, such as dendritic cells, CD4 and CD8 T cells and their effector memory subpopulations, CD4 regulatory T cells, B cells and cytokine IL-6, exhibited statistically significant circadian rhythmicity. In a comparison with historical healthy control individuals, but using shipped samples, we observed that participants with type 1 diabetes had statistically significant phase shifts occurring in the time of peak occurrence of B cells (+4.8 h), CD4 and CD8 T cells (~ +5 h) and their naive and effector memory subsets (~ +3.3 to +4.5 h), and regulatory T cells (+4.1 h). An independent streptozotocin murine experiment confirmed the phase shifting of CD8 T cells and suggests that circadian dysrhythmia in type 1 diabetes might be an effect and not a cause of the disease.CONCLUSIONS/INTERPRETATION: Future efforts investigating this newly described aspect of type 1 diabetes in human participants are warranted. Peripheral immune populations should be measured near the same time of day in order to reduce circadian-related variation.

AB - AIMS/HYPOTHESIS: The circadian clock influences both diabetes and immunity. Our goal in this study was to characterise more thoroughly the circadian patterns of immune cell populations and cytokines that are particularly relevant to the immune pathology of type 1 diabetes and thus fill in a current gap in our understanding of this disease.METHODS: Ten individuals with established type 1 diabetes (mean disease duration 11 years, age 18-40 years, six female) participated in a circadian sampling protocol, each providing six blood samples over a 24 h period.RESULTS: Daily ranges of population frequencies were sometimes large and possibly clinically significant. Several immune populations, such as dendritic cells, CD4 and CD8 T cells and their effector memory subpopulations, CD4 regulatory T cells, B cells and cytokine IL-6, exhibited statistically significant circadian rhythmicity. In a comparison with historical healthy control individuals, but using shipped samples, we observed that participants with type 1 diabetes had statistically significant phase shifts occurring in the time of peak occurrence of B cells (+4.8 h), CD4 and CD8 T cells (~ +5 h) and their naive and effector memory subsets (~ +3.3 to +4.5 h), and regulatory T cells (+4.1 h). An independent streptozotocin murine experiment confirmed the phase shifting of CD8 T cells and suggests that circadian dysrhythmia in type 1 diabetes might be an effect and not a cause of the disease.CONCLUSIONS/INTERPRETATION: Future efforts investigating this newly described aspect of type 1 diabetes in human participants are warranted. Peripheral immune populations should be measured near the same time of day in order to reduce circadian-related variation.

KW - circadian ryhtms

KW - type 1 diabetes

U2 - 10.1007/s00125-021-05468-6

DO - 10.1007/s00125-021-05468-6

M3 - Article

C2 - 34003304

SN - 0012-186X

JO - Diabetologia

JF - Diabetologia

ER -

Peripheral immune circadian variation, synchronisation and possible dysrhythmia in established type 1 diabetes

Abstract

Keywords

UN SDGs

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