008 Metabolic and functional dysregulation of tissue-specific human regulatory T cells in chronic inflammatory diseases

Regulatory T cells (Treg) are a critical immune component guarding against excessive inflammatory responses, but current understanding of Treg heterogeneity and function in non-lymphoid tissue humans is limited. In this project we characterising unique types signatures the context tissue-confined responses human skin gut. We hypothesising that common ground between these pathologies may be found dysfunction regulation. To investigate this, utilizing transcriptomic, phenotypic metabolomic methods, using an integrative bioinformatical approach single-cell (sc) sequencing data global screens Tregs from blood patients with chronic diseases. ScRNA-sequencing diagnosed psoriasis, cutaneous sarcoidosis, ulcerative colitis have shown diseased tissue-Tregs strong tissue-resident signature. exacerbated expression polyamine catabolic genes linked to more activated phenotype compared their healthy counterparts. Additionally, performed untargeted metabolomics blood-derived Tregs, identifying further changes metabolites downstream several nitrogen metabolic pathways nucleotide synthesis. Together, our results indicate novel interface catabolism pyrimidine synthesis inflammation. Ultimately, findings will significantly contribute basic shed light on regulation during