Microbiota-T cell interactions - antigen-specificity and regulation in health and disease | MicroT | Proyecto | Ficha informativa | HORIZON | CORDIS

Objetivo

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.