Regulatory T cells (TREG) are critical players in the control of innate and adaptive immune responses while impacting as well on the functional output of parenchyma tissues. This later effect is exerted by tissue-resident TREG, via an ill-defined mechanism that modulates tissue damage control, that is, a protective response of parenchyma tissues that limits cellular dysfunction and/or damage imposed by inflammation and immunity. The central hypothesis to be tested under this proposal is that tissue-resident TREG modulate tissue damage control via a number of adaptive responses to cellular stress, which preserve the functional outputs of parenchyma tissues. Failure of tissue-resident TREG to modulate adaptive responses to oxidative and hypoxic stress should exacerbate the deleterious effects imposed by these forms of stress on parenchyma cells and as such promote the pathogenesis of immune mediated
inflammatory diseases. This project will address mechanistically how TREG receive signals from tissues exposed to oxidative and hypoxic stress and migrate to those tissues to modulate oxidative and hypoxic stress responses as to dampen tissue damage.
REGDAM will support the development of basic/translational biological knowledge related the impact exerted by immunoregulatory mechanisms on homeostasis and in particular on the function of parenchyma tissues. This should reveal new therapeutic approaches against a broad range of diseases with major morbidity and mortality. These include autoimmunity, metabolic disorders, neurological conditions or infectious diseases, where deregulated inflammation and immunity are the underlying cause of disease. REGDAM addresses a “hot” topic in immunology research, namely the mechanism of action of TREG cells. The uniqueness and hence the competitive edge of REGDAM is to integrate TREG cells cells into the physiologic context of tissue damage control which to the best of our knowledge has not been done before. REGDAM should reveal important knowledge for academia as well as for clinical research and practice, with concrete benefits for the European economy and society in general.
