Nov 29: Tissue T cell adaptation in homeostasis and inflammation
T cells in tissue microenvironments are highly adaptable, with local cues driving differentiation, functioning and maintenance of these T cells. This adaptation is tightly regulated within a microenvironment. However, striking overlap in transcriptional and phenotypical programming can be observed, especially in non-homeostatic conditions such as inflammation. These were the main conclusions of Lisanne Lutter in her PhD thesis that shed defended on November 29, 2022.
Chronic inflammatory disorders such as juvenile idiopathic arthritis and Crohn’s disease are characterized by a relapsing-remitting pattern of inflammation. Many therapeutic options are aimed at suppressi ng the immune system. It is not known, however, how (regulatory) T cells are programmed and adapt during inflammation, and therefore what we can best target therapeutically. In her PhD thesis, Lisanne Lutter (Center for Translational Immunology, UMC Utrecht) investigated how regulatory T cells, which suppress the immune system, adapt to the environment of residence.
Lisanne Lutter and co-investigators showed in her PhD research that regulatory T cells acquire an overarching activated and highly suppressive profile irrespective of the type of inflammation, e.g. auto-inflammation in juvenile idiopathic arthritis or inflammation in cancer. The local environment further refines the profile with environment-specific markers for optimal local functioning. Moreover, they have studied how T cells adapt to the epithelium and lamina propria of the intestine. The profile of these cells completely differs even though these environments are separated by a basement membrane of only 7 µm.
T cells in the epithelium have the ability to quickly react but also express many regulatory markers translating to an ‘activated-yet-resting’ profile. T cells in the lamina propria have an activated profile with cytokine and granzyme production to quickly react to stimuli. During inflammation in Crohn’s disease the cells in the epithelial layer acquire a profile similar to cells in the lamina propria, which could potentially prolong inflammation. As tissue-specific and potentially pathogenic cells, intra-epithelial T cells are a potential target for therapeutic intervention in chronic tissue-specific inflammatory diseases such as inflammatory bowel disease.
Lisanne Lutter concluded that the tissue location of a T cell is the main determinant of its profile. The results obtained in this research broadens the understanding of local programming and adaptation of the immune system.
PhD defense
Lisanne Lutter (1990, Haarlem) defended her PhD thesis on November 29, 2022 at Utrecht University. The title of her thesis was “Let’s be adaptable - Tissue T cell adaptation in homeostasis and inflammation.” Supervisors were prof. dr. Femke van Wijk (Center for Translational Immunology, UMC Utrecht) and prof. dr. Bas Oldenburg (Department of Gastroenterology and Hepatology, UMC Utrecht). In July 2022, Lisanne started her residency in pathology at the Amsterdam University Medical Center, the Netherlands.