ENLIGHT-TENplus · European Network Linking Informatics and Genomics of Helper T cells in Tissues

European Network Linking Informatics and Genomics of Helper T cells in Tissues

Autoimmune diseases arise from aberrant immune responses against the body’s own tissues. There are more than 80 different types of autoimmune disease affecting various organs, and their prevalence is increasing. Recent findings suggest that the chronic nature of autoimmune diseases largely depends on the reactivation of tissue-resident memory T (TRM) cells, which are present in almost all tissues in the body. Therefore, TRM cells are a key target in the development of precision diagnostic and therapeutic strategies for autoimmune diseases. TRM cells are strongly influenced by the ‘conditioning’ in the tissue. In healthy individuals, this conditioning tailors the immune response to the precise needs of organ-specific defence. However, in patients with chronic autoimmune diseases, environmental conditioning can modulate an ongoing tissue-resident memory response, triggering unexpected pathology. The molecular factors controlling tissue-specific conditioning and the reactivation of TRM cells in the context of autoimmunity are often poorly understood, as the interaction between TRM cells and their microenvironment is extremely complex. Consequently, there is an urgent need to apply cellular immunology and omics approaches to TRM cells derived from steady-state and autoimmune conditions to improve our understanding of their identity and function and fully realise their therapeutic potential. However, a crucial missing link in the current research environment is the lack of qualified individuals with the cellular and molecular immunology skills to recognise and define important scientific questions that can be answered using omics approaches, as well as the bioinformatics expertise to analyse and interpret the resulting Big Data. Consequently, although large datasets can be acquired on particular TRM cell populations, they cannot be utilised optimally due to a lack of bioinformatics expertise. The ENLIGHT-TEN+ project (European Network Linking Informatics and Genomics of Helper T cells in Tissues comprising TEN European countries) aimed to train a cohort of early-stage researchers (ESRs) with an in-depth understanding of T cell immunology and expertise in the bioinformatic processing of large datasets. ENLIGHT-TEN+ had the following major objectives: - Integrate cross-disciplinary, highly innovative technologies to generate a novel view of TRM cells, understanding the microenvironmental cues and molecular factors that shape their unique functional properties with unprecedented resolution. - Apply this understanding to immune-mediated pathologies, enabling selective manipulation of TRM cells in autoimmune diseases. - Foster a new generation of enthusiastic young researchers who can analyse Big Data and implement novel concepts of T cell biology in biomedical applications. In conclusion, the programme equipped ESRs with in-depth scientific training and advanced technological skills, as well as broad exposure to experimental and computational approaches in T cell research. The findings have significantly advanced our understanding of TRM cell biology and pathology, while generating innovative tools and datasets that will support the development of future therapies for immune-related diseases.

Data: CORDIS, © European Union