Keywords: Transplant Immunology, Type 1 Diabetes, T cells, Immunological Tolerance
Organ transplantation remains the only life-saving procedure for most cases of organ failure. Unfortunately, despite decades of research, transplantation remains a treatment, not a cure. The overarching goal of the Raimondi Team, within the Vascularized Composite Allostransplantation Laboratory, is to employ multidisciplinary approaches to improve our understanding of transplant rejection and develop innovative immunomodulatory strategies to promote immunological tolerance. We believe an undervalued area of investigation is the impact of inflammatory cytokines on the activation of T cells. In addition to the classic dogma that cytokines determine the skewing of effector T cells, they can interfere with regulatory mechanisms that are normally in place to control immunity (e.g. regulatory T cell activity). Moreover, inflammatory cytokines can also directly provide costimulatory signals. By juxtaposing investigations in transplantation and in the tangential area of autoimmune diabetes, we aim at clarifying the interplay between pro- and anti-inflammatory cytokines in the activation of pathogenic T cells. We dynamically integrate this constantly improving knowledge into exciting collaborations with material scientists and protein engineers to deploy advanced drug delivery strategies and biomimetic strategies to achieve a better control of immune activation. Such approaches range from the localized inhibition of cytokine signaling via nanoparticles or injectable hydrogels, to the engineering of artificial antigen presenting cells that engage regulatory T cells or the optimization of CAR-Treg-based applications. We are also interested in exploring unconventional approaches to modulate immunity, like our ongoing exploration of the modulation of thymic epithelial cell populations to alter the process of thymic selection. Ultimately, the development of innovative immunomodulatory strategies gives us novel tools to go back to address basic immunological questions in an exciting feedforward loop.
Publications and Interests: https://jhu.pure.elsevier.com/en/persons/giorgio-raimondi