Blockade of TIM-1 on the donor graft ameliorates graft-versus-host disease following hematopoietic cell transplantation

Iliopoulou, Bettina P.; Hsu, Katie; Pérez-Cruz, Magdiel; Tang, Sai-Wen; Pang, Wendy W.; Erkers, Tom; Kambham, Neeraja; Freeman, Gordon J.; Meyer, Everett

doi:10.1182/bloodadvances.2019000286

Cited by 5 publications

(6 citation statements)

References 34 publications

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“…On the whole, TIM-1 today ranks among the critical immune checkpoints which may serve as targets for therapeutic action aimed, inter alia, at the activation of antitumor immune reactions [52][53][54].…”

Section: Kim-1 and Immune Reactionsmentioning

confidence: 99%

Kidney Injury Molecule 1 (KIM-1): a Multifunctional Glycoprotein and Biological Marker (Review)

Karmakova¹,

Сергеева²,

Kanukoev³

et al. 2021

Sovrem Tehnol Med

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KIM-1 (kidney injury molecule 1) is a transmembrane glycoprotein also known as HAVcr-1 and TIM-1 belongs to the T-cell immunoglobulin and mucin domain family (TIM) of proteins. TIM glycoproteins are presented on the immune cells and participate in the regulation of immune reactions. KIM-1 differs from other members of its family in that it is expressed not only by immunocompetent cells but epithelial cells as well. Cellular and humoral effects mediated by KIM-1 are involved in a variety of physiological and pathophysiological processes.Current understanding of the mechanisms determining the participation of KIM-1 in viral invasion, the immune response regulation, adaptive reactions of the kidney epithelium to acute ischemic or toxic injury, in progression of chronic renal diseases, and kidney cancer development have been presented in this review. Data of clinical researches demonstrating the association of KIM-1 with viral diseases and immune disorders have also been analyzed. Potential application of KIM-1 as urinary or serological marker in renal and cardiovascular diseases has been considered.

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Section: Kim-1 and Immune Reactionsmentioning

confidence: 99%

Kidney Injury Molecule 1 (KIM-1): a Multifunctional Glycoprotein and Biological Marker (Review)

Karmakova¹,

Сергеева²,

Kanukoev³

et al. 2021

Sovrem Tehnol Med

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“…Higher TIM-1 expression in cancer tissues may be used as an independent prognostic predictor for patients. Increased expression of TIM-1 is also linked to T cell immune tolerance (33, 34). Therefore, the increased expression of TIM-1 is the result of organismal or viral regulation in the specific situation.…”

Section: Discussionmentioning

confidence: 99%

Japanese Encephalitis Virus NS1’ Protein regulates the expression and distribution of TIM-1 to promote viral infection

Liang¹,

Xie²,

Pan³

et al. 2022

Preprint

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Japanese encephalitis virus (JEV) is a mosquito-borne Flavivirus, which may cause severe encephalitis in humans, horses, and other animals. TIM-1 has been identified to be a receptor that promotes various viruses to enter into target cells in recent years. In the present study, we found that TIM-1 protein was significantly increased in A549 cells at the late stage of JEV infection, while the transcription levels of TIM-1 remained unaltered. Interestingly, we found that NS1’ protein plays a key role in increasing the expression of TIM-1 in cells infected with JEV. Further, we found that the NS1’ protein also efficiently regulates TIM-1 protein to distribute in the cytoplasm in JEV-infected cells, and the amount of TIM-1 protein located on the cell membrane was reduced instead. As a consequence, NS1’ protein antagonize TIM-1 mediated viral restriction for further viral infection and propagation in the late stage of infection. In molecular mechanism, the molecular weight of TIM-1 increased a bit in the present of NS1’. Expression of NEU1 down-regulated TIM-1 expression and oseltamivir treatment increased the expression of TIM-1. Therefore, our data indicated that JEV NS1’ protein facilitated the sialylation modification of TIM-1 to up-regulate the level of TIM-1 expression and regulate its distribution. Collectively, our study revealed that JEV NS1’ protein regulates the expression and distribution of TIM-1 by facilitating its sialylation to antagonize TIM-1-mediated JEV restriction for further infection. Understanding the functional interplays between TIM-1 and NS1’ proteins will offer new insights into virus-host interaction.

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“…Inhibition of CD38 also resulted in reduced clinical and histological GVHD [ 142 ]. Likewise, blockade of inducible T cell co-stimulator (ICOS; CD278) and T cell immunoglobulin and mucin -1 (TIM-1; CD365), co-stimulatory molecules present on T cells, by neutralising mAbs can also reduce GVHD in humanised mice [ 143 , 144 ]. Collectively, these studies reveal roles for activation of each of these co-stimulatory molecules in the promotion of GVHD.…”

Section: Cell Signalling Mechanisms In Gvhdmentioning

confidence: 99%

Insights into mechanisms of graft-versus-host disease through humanised mouse models

et al. 2022

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Graft-versus-host disease (GVHD) is a major complication that occurs following allogeneic haematopoietic stem cell transplantation (HSCT) for the treatment of haematological cancers and other blood-related disorders. GVHD is an inflammatory disorder, where the transplanted donor immune cells can mediate an immune response against the recipient and attack host tissues. Despite over 60 years of research, broad-range immune suppression is still used to prevent or treat GVHD, leading to an increased risk of cancer relapse and infection. Therefore, further insights into the disease mechanisms and development of predictive and prognostic biomarkers are key to improving outcomes and reducing GVHD development following allogeneic HSCT. An important preclinical tool to examine the pathophysiology of GVHD, and to understand the key mechanisms that lead to GVHD development, are preclinical humanised mouse models. Such models of GVHD are now well-established and can provide valuable insights into disease development. This review will focus on models where human peripheral blood mononuclear cells are injected into immune-deficient non-obese diabetic (NOD)-scid-interleukin-2(IL-2)Rγ mutant (NOD-scid-IL2Rγnull) mice. Humanised mouse models of GVHD can mimic the clinical setting for GVHD development, with disease progression and tissues impacted like that observed in humans. This review will highlight key findings from preclinical humanised mouse models regarding the role of donor human immune cells, the function of cytokines and cell signalling molecules and their impact on specific target tissues and GVHD development. Further, specific therapeutic strategies tested in these preclinical models reveal key molecular pathways important in reducing the burden of GVHD following allogeneic HSCT.

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Blockade of TIM-1 on the donor graft ameliorates graft-versus-host disease following hematopoietic cell transplantation

Abstract: Key Points Administration of anti–TIM-1 blocking mAb ameliorates acute GVHD while preserving graft-versus-tumor effects. Treatment with anti–TIM-1 blocking mAb does not affect proliferation of donor allogeneic T cells.

Cited by 5 publications

References 34 publications

Kidney Injury Molecule 1 (KIM-1): a Multifunctional Glycoprotein and Biological Marker (Review)

Kidney Injury Molecule 1 (KIM-1): a Multifunctional Glycoprotein and Biological Marker (Review)

Japanese Encephalitis Virus NS1’ Protein regulates the expression and distribution of TIM-1 to promote viral infection

Insights into mechanisms of graft-versus-host disease through humanised mouse models

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