Summary
The skin is the largest organ of the body and represents the primary physical barrier to the environment. Circadian, ~24h rhythms in the environment have emerged as important regulators of the immune system, yet, the circadian dynamics of leukocyte turnover and function in the skin are completely unknown. Insights into the mechanisms occurring at this host-environment interface will be of key importance to understand how rhythmicity in the immune system is achieved. This will produce knowledge to optimize adjuvant design and maximize adaptive immune responses such as required in vaccinations, ultimately providing a time window for therapy.
We will elucidate how circadian dynamics in leukocyte input and output to the skin interplay to create oscillatory numbers of leukocytes in this tissue. We will assess the impact of lineage-specific rhythmicity and arrhythmicity on skin immune homeostasis using an innovative combination of novel genetic tools. We will mechanistically assess how circadian leukocyte dynamics in the skin are governed at a higher level by the sympathetic nervous system. We will finally unravel the cause and the functional relevance of circadian leukocyte dynamics in the skin by assessing whether they primarily represent a response to exogenous factors or whether they are caused by physiological tissue turnover in response to daily recurring mechanical stress. Based on these data we will create a mathematical model determining circadian skin leukocyte turnover in a quantitative manner.
The project combines the disciplines of immunology and chronobiology by obtaining unprecedented insights into circadian immunity in the skin, a critical epithelial barrier site, which is of broad impact for both fields. Our extensive experience in the rhythmic control of both the innate and adaptive immune system makes us well poised to unravel the molecular mechanisms that orchestrate circadian leukocyte dynamics in the skin.
We will elucidate how circadian dynamics in leukocyte input and output to the skin interplay to create oscillatory numbers of leukocytes in this tissue. We will assess the impact of lineage-specific rhythmicity and arrhythmicity on skin immune homeostasis using an innovative combination of novel genetic tools. We will mechanistically assess how circadian leukocyte dynamics in the skin are governed at a higher level by the sympathetic nervous system. We will finally unravel the cause and the functional relevance of circadian leukocyte dynamics in the skin by assessing whether they primarily represent a response to exogenous factors or whether they are caused by physiological tissue turnover in response to daily recurring mechanical stress. Based on these data we will create a mathematical model determining circadian skin leukocyte turnover in a quantitative manner.
The project combines the disciplines of immunology and chronobiology by obtaining unprecedented insights into circadian immunity in the skin, a critical epithelial barrier site, which is of broad impact for both fields. Our extensive experience in the rhythmic control of both the innate and adaptive immune system makes us well poised to unravel the molecular mechanisms that orchestrate circadian leukocyte dynamics in the skin.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101001233 |
| Start date: | 01-10-2021 |
| End date: | 30-09-2026 |
| Total budget - Public funding: | 1 999 963,00 Euro - 1 999 963,00 Euro |
Cordis data
Original description
The skin is the largest organ of the body and represents the primary physical barrier to the environment. Circadian, ~24h rhythms in the environment have emerged as important regulators of the immune system, yet, the circadian dynamics of leukocyte turnover and function in the skin are completely unknown. Insights into the mechanisms occurring at this host-environment interface will be of key importance to understand how rhythmicity in the immune system is achieved. This will produce knowledge to optimize adjuvant design and maximize adaptive immune responses such as required in vaccinations, ultimately providing a time window for therapy.We will elucidate how circadian dynamics in leukocyte input and output to the skin interplay to create oscillatory numbers of leukocytes in this tissue. We will assess the impact of lineage-specific rhythmicity and arrhythmicity on skin immune homeostasis using an innovative combination of novel genetic tools. We will mechanistically assess how circadian leukocyte dynamics in the skin are governed at a higher level by the sympathetic nervous system. We will finally unravel the cause and the functional relevance of circadian leukocyte dynamics in the skin by assessing whether they primarily represent a response to exogenous factors or whether they are caused by physiological tissue turnover in response to daily recurring mechanical stress. Based on these data we will create a mathematical model determining circadian skin leukocyte turnover in a quantitative manner.
The project combines the disciplines of immunology and chronobiology by obtaining unprecedented insights into circadian immunity in the skin, a critical epithelial barrier site, which is of broad impact for both fields. Our extensive experience in the rhythmic control of both the innate and adaptive immune system makes us well poised to unravel the molecular mechanisms that orchestrate circadian leukocyte dynamics in the skin.
Status
SIGNEDCall topic
ERC-2020-COGUpdate Date
27-04-2024
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