Moreover, the wide application of IPC in clinical practice is limited because of the direct mechanical trauma to major vascular structures, the unpredictability of the ischemic episode, and for ethical reasons. ischemia-reperfusion injury (IRI) Introduction Hepatitis B computer virus infection is highly prevalent in China, which could lead to more than five million patients developing irreversibly decompensated liver cirrhosis and even hepatocellular carcinoma (HCC) [1]. Liver transplantation (LT) is considered the best life-saving therapy. However, a serious shortage of donor livers is the main limit for the survival rate of patients on the waiting list for an LT. To solve this issue, several transplant centers use donor livers that exceed traditional criteria, including age beyond 60, prolonged time of warm and chilly storage, and macrovesicular steatosis beyond 30% [2]. These marginal livers are particularly sensitive to ischemia reperfusion injury (IRI), which leads to frequent main graft non-function and promotes the progression of acute or chronic rejection [3]. Furthermore, IRI also causes damage to other organs, such as acute kidney injury [4], which is a fatal complication [5]. As early as 1986, Murry et al. confirmed that this multiple brief ischemic episodes that precede myocardial infarction were beneficial to protect the myocardium from coronary occlusion [6]. Currently, accumulating evidence shows that ischemic preconditioning (IPC) increases liver resistance to IRI and longer ischemia [7-10]. However, few studies have focused on the molecular mechanism of IPC. Moreover, the wide application of IPC in clinical practice is limited because of the direct mechanical trauma to major vascular structures, the unpredictability of the ischemic episode, and for ethical reasons. Especially in China, the donor livers are harvested mainly from donations from deceased cardiac patients. Despite remote ischemic conditioning being considered as an alternative choice that could protect kidneys from IRI after LT, it offered no protective effect on graft function [11]. In this regard, further investigation of the molecular mechanism of IPC is required urgently. Recently, several studies reported that this T cell Immunoglobulin and Mucin domain-containing molecules-1 (TIM-1) was responsible for activation of various myeloid leukocytes [12]. TIM-1 belongs to the TIM gene family and is located on human chromosome Midecamycin 5q33.2 in a region that is correlated significantly with allergy, asthma, and autoimmunity [13,14]. Moreover, TIM-1 is usually a pattern acknowledgement receptor that recognizes phosphatidylserine (PtdSer) [15] expressed on activated CD4+ T cells, and sustains preferentially the expression of Th2, but no or little expression of Th1 and Th17 after differentiation [16]. Crosslinking of TIM-1 with its ligand or agonist monoclonal antibody provided a potent co-stimulatory signal to increase the proliferation of na?ve T cells and interleukin (IL)-4 production of Th2 cells [16]. In GAQ addition, the conversation of TIM-1 with TIM-2, TIM-3, or TIM-4 is also involved in regulating Th1, and certain dendritic cells and macrophages via PtdSer uncovered on exosomes [17]. TIM-1 is also called known as kidney injury molecule (KIM-1), whose expression is localized specifically around Midecamycin the regenerating proximal tubule epithelial cells and is apparently upregulated in the post-ischemic rat kidney [18]. Previously, in the IRI model with LT, we found that TIM-1 expression increased in the liver with IRI, and TIM-1 blockage overcame IRI by decreasing TGF- and IFN- expression, and increasing the expression of IL-4, IL-10, and IL-22 [19]. Furthermore, the use of an antagonistic anti-TIM-1 antibody Midecamycin decreased hepatocellular apoptosis and improved liver function by inhibiting local neutrophil infiltration, and sequestration of macrophages and T lymphocytes in LT [20]. This evidence implied that TIM-1 plays a crucial role in the activation and differentiation of T cell and immunity-mediated IRI. Midecamycin Here, we provide evidence that suppression of TIM-1 signaling is essential for the IPC-mediated decreases in IRI damage in LT. Material and methods Animals Male C57BL/6 mice (5-week-old, 18-22.