Defective KIM-1 phagocytosis does not predispose to acute graft dysfunction after kidney transplantation in humans

Suri, Rita S.; Lee, Ji Yun; Ban, Matthew R.; Shrum, Bradly; Tutunea-Fatan, Elena; Ismail, Ola Z.; Leckie, Steven; McIntyre, Adam D.; Xu, Qingyong; Lee, Seung Ho; Chickera, Sonali de; Hegele, Robert A.; Gunaratnam, Lakshman

doi:10.1016/j.kint.2022.05.006

Cited by 1 publication

(1 citation statement)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Significant gaps remain on the biology of KIM-1/TIM-1 in vivo, so far limiting the use of KIM-1-based biomarker and/or therapeutics in clinical medicine. 79,88,[177][178][179][180][181] This is particularly true in the kidney where the prevailing renoprotective role of KIM-1 in AKI has been put into question. 17,69 Although a majority of studies have investigated the tissue-specific roles of KIM-1/TIM-1, more work is needed to better understand the interaction between KIM-1/TIM-1 in the parenchyma and the immune system.…”

Section: Future Directionsmentioning

confidence: 99%

Sensing Dying Cells in Health and Disease

Tutunea-Fatan,

Arumugarajah,

Suri

et al. 2024

JASN

Self Cite

View full text Add to dashboard Cite

Kidney Injury Molecule-1 (KIM-1), also known as T cell immunoglobulin and mucin domain-1 (TIM-1), is a widely recognized biomarker for acute kidney injury, but its biological function is less appreciated. KIM-1/TIM-1 belongs to the TIM family of conserved transmembrane proteins which bear the characteristic six-cysteine immunoglobulin-like (IgV) domain. The latter enables binding of KIM-1/TIM-1 to its natural ligand, phosphatidylserine, expressed on the surface of apoptotic cells and necrotic cells. KIM-1/TIM-1 is expressed in a variety of tissues and plays fundamental roles in regulating sterile inflammation and adaptive immune responses. In the kidney, KIM-1 is upregulated on injured renal proximal tubule cells transforming them into phagocytes for clearance of dying cells and helps to dampen sterile inflammation. TIM-1 expressed in T cells, B cells, and Natural Killer T (NKT) cells, is essential for cell activation and immune regulatory functions in the host. Functional polymorphisms in the gene for KIM-1/TIM-1, HAVCR1, have been associated with susceptibility to immunoinflammatory conditions, and Hepatitis A virus-induced liver failure which is thought to be due to a differential ability of KIM-1/TIM-1 variants to bind phosphatidylserine. This review will summarize the role of KIM-1/TIM-1 in health and disease, and its potential clinical applications as a biomarker and therapeutic target in humans.

show abstract