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Control Immune Response by Regulatory T-Cells - DR SHIMON SAKAGUCHI

Regulatory T (Treg) cells, which are expressing the transcription factor Foxp3 in the nucleus, CD25 and CTLA-4 on the cell surface, are actively engaged in the maintenance of immunological self-tolerance and homeostasis. For example, mutations of the Foxp3 gene causes Treg cell deficiency, culminating in IPEX syndrome accompanying various autoimmune diseases, allergy, and immunopathology such as inflammatory bowel disease. Furthermore, many single nucleotide polymorphisms in Treg signature gene loci contribute to genetic susceptibility to a variety of immunological diseases via affecting Treg cell development and function. Therapeutically, depletion or functional impairment of Treg cells is able to enhance cancer and microbial immunity, while their numerical expansion or functional augmentation is instrumental in treating autoimmune disease and establishing graft tolerance. We have recently made attempts to pharmacologically control Treg-specific transcriptional and epigenetic changes and thereby control Treg cell development and function. We found that certain tyrosine kinase inhibitors that blocked T-cell receptor-proximal signaling in T cells were able to specifically deplete mature Treg cells, thereby enhancing tumor immunity in humans. On the other hand, inhibitors of a serine threonine kinase involved in a T-cell signaling pathway evoked Foxp3 expression in conventional T cells including effector/memory T cells and converted them to functionally competent Treg-like cells, which effectively suppressed autoimmune disease and allergy in animal models. It will be discussed how the development and function of Treg cells can be controlled by transcriptional and epigenetic interventions and how Treg cells be pharmacologically targeted to control a variety of physiological and pathological immune responses.

🗓Tuesday, 30th March

⏰9-11AM GMT+1 (UK Time)

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