In vivo, TIM-1 is expressed on splenic B cells and is a marker for the identification of IL-10+ regulatory B cells (6, 7). TIM-1 is also expressed on CD4+ T cells, mast cells, invariant NKT (iNKT) cells, dendritic cells, kidney epithelium and a broad range of mucosal epithelium (4, 8-15). The expression of TIM-1 is upregulated on activated Th2 cells, after dendritic cell maturation, and on kidney tubular epithelial cells after injury (4, 9, 13, 14, 16, 17). Metalloproteinase-mediated cleavage of TIM-1 at the membrane-proximal region results in the release of a soluble form of TIM-1 which is detectable in the urine and in circulation (18, 19). Urinary TIM-1 is highly elevated in nephropathy and may be a useful biomarker for renal damage (16, 20 - 25).
TIM-1 has been reported to be a receptor for a number of ligands, including phosphatidylserine, leukocyte mono-immunoglobulin-like receptor 5 (LMIR5/CD300b), TIM-1 (homophilic), TIM-4, IgA, and the glycoproteins of a number of enveloped viruses (5, 15, 26-33). Its interaction with phosphatidylserine enables TIM-1 to mediate the phagocytosis of apoptotic cells (26-28). In TIM-1-bearing iNKT cells, interaction with apoptotic cells can also result in iNKT cell activation, proliferation, and cytokine production (11). Interactions between cell-surface or soluble TIM-1 with LMIR5 is proposed to induce LMIR5-mediated activation of myeloid cells including macrophages/monocytes, mast cells, neutrophils, and dendritic cells (29). These interactions contribute to tissue homeostasis and damage during kidney injury (29). Ligandinduced TIM-1 signaling costimulates T cell activation and enhances Th2 cytokine production (9, 31, 34). In humans, TIM-1 serves as a cellular entry receptor for various viruses, including hepatitis A virus, Ebolavirus and Marburgvirus (15, 33).
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