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Presenter: Yuan, Zhai, Los Angeles, United States
Authors: Yuan Zhai
IRI is associated with multiple clinical settings and remains to be the major limiting factor in liver transplantation. No effective and specific therapies are current available. Since IR-triggered tissue inflammation is the major driving force of the development of full scale of IRI, we have been studying mechanisms of liver immune activation by IR. By gene array analysis of ischemic liver tissues early after reperfusion, we have identified critical biological pathways associated with graft failure. Among them, the TLR4-type I interferon and CXCL10 pathway plays an essential role in the activation of liver immune response against IR and may link the interaction of liver innate and adaptive immune systems. Although liver IRI occurs in the absence of exogenous Ags, CD4 T cells are critically involved in liver tissue inflammation. By dissecting the functional mechanism of CD4 T cells, we have demonstrated a new paradigm of adaptive T cell regulation of innate immune response by reverse signaling via CD154-CD40 pathway in an Ag-non-specific manner in liver IRI. These studies shall provide us rationales to design novel therapeutic strategies to ameliorate liver IRI in clinical patients.
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