Skin-resident memory T (TRM) cells persist long-term in the skin to provide immune protection. However, their activation by allergens or autoantigens can cause chronic inflammatory skin disease. Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are common T cell-driven diseases in which TRM cells play a key role and contribute to their chronicity. Current treatments suppress inflammation, but fail to cure patients long-term. Thus, there is a need for a better understanding of pathogenic TRM in TH2-driven skin disease, such as AD and ACD, as a prerequisite for the development of curative therapies.
New evidence suggests that PPAR-γ constitutes a link between TRM and TH2-driven skin disease, which is of major interest given the large potential of targeting PPAR-γ for therapeutic purposes. Interestingly, mouse models suggest that both pathogenic TH2 cells and skin TRM critically depend on PPAR-γ. Yet, the importance and function of PPAR-γ in human skin TH cells remain unknown. Our research aims to elucidate the functional importance of PPAR-γ for TH2 cells in human skin to develop curative rather than merely suppressive treatments for chronic inflammatory skin disease.
Intricacies of IL-9R signaling in human T helper cells
Skin-homing pathogenic TH2 cells that participate in inflammatory and malignant skin diseases are characterized by high expression of both interleukin 9 (IL-9) and its receptor, IL-9R. The focus of one of our research projects is to elucidate the function of autocrine and paracrine IL-9 in skin inflammation and to evaluate the potential of its therapeutic manipulation.
TH9 cells depend on cystine uptake and PPAR-γ signaling to prevent unchecked lipid ROS and cell death
PPAR-γ is a regulator of amino acid metabolism in human TH9 cells, which specifically depend on cystine for control of lipid peroxidation and bioenergetic homeostasis. Interference with either cystine metabolism or PPAR-γ might open up therapeutic avenues in the context of type 2 inflammatory diseases, which we investigate in one of our research projects.
Functional role of IL-18 in atopic dermatitis
Pathogenic TH2 cells are crucial contributors to the pathogenesis of AD by secreting high levels of IL-13 and IL-22, however, the upstream regulators of pTh2 cells in AD skin remain incompletely understood. IL-18 is one such putative regulator and is linked to AD pathogenesis by multiple lines of evidence raising intriguing questions regarding its role in the activation of pTh2 cells in AD skin, which we investigate in one of our research project.
Control of skin T cell function by AhR agonism
The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor and driver of inflammatory skin diseases such as psoriasis and atopic dermatitis. The effects of AhR ligation on T cells in the setting of an inflammatory skin disease is not yet fully understood. We therefore aim to characterize the effects of AhR ligations as a potential therpeutical target for inflammatory skin diseases.
