Summary
The microbiota has an enormous influence on human health. CD4+ T cells play a central role in controlling the interaction with the microbiota. By specifically reacting against individual microbial species, T cells enable a mutualistic co-existence with microbes. Inappropriate T cell responses against microbes are in turn associated with inflammatory diseases. Thus, the combination of T cell specificity and functionality form the key determinant for physiological versus pathological host-microbiota interactions. So far, research on T cell-microbiota interaction is almost exclusively focussed on functional T cell subsets, whereas antigen-specificity is rarely addressed. This is a significant roadblock for developing targeted therapeutic interventions for microbiota-associated diseases.
The interaction with the microbiota poses two particular challenges for adaptive immunity: first, the extremely high diversity of microbial species, and thus potential T cell targets; second, microbes are persistent and thus probably encountered chronically. Currently, we do not know (1) which microbes are targets of specific T cell reactivity in humans, (2) how the (chronic) interaction with the huge number of different microbial species is regulated by T cell specificity and function, and (3) how alterations of these parameters contribute to microbiota-associated diseases.
I developed a highly sensitive technology to detect and deeply characterize microbe-specific T cells directly from human samples. MicroT will identify microbial target species of human T cells and unravel the molecular mechanisms regulating chronic interaction of T cells with the highly diverse microbiota. I will define the impact of specific T cell-microbiota interactions on chronic inflammatory diseases and upon ageing. Answering these fundamental questions of microbiota-T cell interaction will identify specific immune or microbial targets as an essential basis for rational development of novel targeted therapies.
The interaction with the microbiota poses two particular challenges for adaptive immunity: first, the extremely high diversity of microbial species, and thus potential T cell targets; second, microbes are persistent and thus probably encountered chronically. Currently, we do not know (1) which microbes are targets of specific T cell reactivity in humans, (2) how the (chronic) interaction with the huge number of different microbial species is regulated by T cell specificity and function, and (3) how alterations of these parameters contribute to microbiota-associated diseases.
I developed a highly sensitive technology to detect and deeply characterize microbe-specific T cells directly from human samples. MicroT will identify microbial target species of human T cells and unravel the molecular mechanisms regulating chronic interaction of T cells with the highly diverse microbiota. I will define the impact of specific T cell-microbiota interactions on chronic inflammatory diseases and upon ageing. Answering these fundamental questions of microbiota-T cell interaction will identify specific immune or microbial targets as an essential basis for rational development of novel targeted therapies.
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| Web resources: | https://cordis.europa.eu/project/id/101040023 |
| Start date: | 01-07-2022 |
| End date: | 30-06-2027 |
| Total budget - Public funding: | 1 500 000,00 Euro - 1 500 000,00 Euro |
Cordis data
Original description
The microbiota has an enormous influence on human health. CD4+ T cells play a central role in controlling the interaction with the microbiota. By specifically reacting against individual microbial species, T cells enable a mutualistic co-existence with microbes. Inappropriate T cell responses against microbes are in turn associated with inflammatory diseases. Thus, the combination of T cell specificity and functionality form the key determinant for physiological versus pathological host-microbiota interactions. So far, research on T cell-microbiota interaction is almost exclusively focussed on functional T cell subsets, whereas antigen-specificity is rarely addressed. This is a significant roadblock for developing targeted therapeutic interventions for microbiota-associated diseases.The interaction with the microbiota poses two particular challenges for adaptive immunity: first, the extremely high diversity of microbial species, and thus potential T cell targets; second, microbes are persistent and thus probably encountered chronically. Currently, we do not know (1) which microbes are targets of specific T cell reactivity in humans, (2) how the (chronic) interaction with the huge number of different microbial species is regulated by T cell specificity and function, and (3) how alterations of these parameters contribute to microbiota-associated diseases.
I developed a highly sensitive technology to detect and deeply characterize microbe-specific T cells directly from human samples. MicroT will identify microbial target species of human T cells and unravel the molecular mechanisms regulating chronic interaction of T cells with the highly diverse microbiota. I will define the impact of specific T cell-microbiota interactions on chronic inflammatory diseases and upon ageing. Answering these fundamental questions of microbiota-T cell interaction will identify specific immune or microbial targets as an essential basis for rational development of novel targeted therapies.
Status
SIGNEDCall topic
ERC-2021-STGUpdate Date
09-02-2023
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