Table 2.
The role of TIM3 in kidney diseases.
| Disease | Cell type of expression | Subject/ model | Function | Ref. |
|---|---|---|---|---|
| Acute kidney injury | monocytes/macrophages | Murine/ IRI | aggravates kidney IR injury via the TLR-4/NF-κB signaling and NLR-C4 inflammasome activation | (74) |
| Treg | Human | lower TIM3 expression in Treg cells restricts the efficacy of Treg response in AKI. | (75) | |
| Kidney transplant | – | Human | Patients of acute and chronic allograft dysfunction have greater urinary and blood TIM3 mRNA expressions. a promising biomarker for noninvasive diagnosis of allograft dysfunction. |
(78, 81) |
| Diabetic kidney disease (DKD) | – | Human; Murine/STZ-induced and db/db mice |
TIM3 expression is increased on renal macrophages in DKD aggravates podocyte injury in DKD by promoting macrophage activation via NF-kB/TNF-α pathway. |
(86) |
| – | Human | Serum GAL9 level in the patient with type 2 diabetes is positively correlated with age, creatinine, urea nitrogen and osmotic pressure and negatively correlated with eGFR. | (87) | |
| IgA nephropathy | – | Human | There is a positive correlation between pathological manifestations and expression degree of TIM3 in IgAN. | (104) |
| Membranous nephropathy | – | Human/serum | Serum TIM3 concentration in patients with MN is considerably higher than that in healthy individuals. TIM3 may be a diagnostic indicator for distinguishing between healthy individuals and patients with MN as well as between different stages of MN. |
(105) |
| Systemic lupus erythematosus /Lupus nephritis | CD4+T, CD8+T, CD56+T | Human | Expression of TIM3 and Gal9 in serum in patients with SLE are significantly higher than those of healthy controls. The up-regulation of TIM3 and Gal9 expression in patients with SLE is closely related to the SLEDAI scores. |
(91) |
| CD3+CD4+T, CD3+CD4-T | Human | Expression of Tim-3 and co-expression of TIM3 and Fas on certain peripheral T subsets are associated with disease activity in SLE patients. | (90) | |
| – | Murine/ pristane-induced model | GAL9 deficiency protects against the development of immune complex glomerulonephritis, arthritis, and peritoneal lipogranuloma formation in pristane-induced lupus model. | (101) | |
| Anti-GBM glomerulonephritis | – | Murine | Administration of GAL9 to anti-GBM GN mice ameliorated renal tubular injury, and reduced the formation of crescents. The protective role of Gal9 in anti-GBM GN is associated with the inhibition of Th1 and Th17 cell-mediated immune responses. |
(103) |
| Myeloperoxidase-ANCA-associated vasculitis | Dendritic cell | Human | Reduced expression of TIM3 and an increased expression of TLR4 are identified on DCs of active MPO-AAV patients. TIM3 plays an important role in maintaining the NETs mediate immune homeostasis in MPO-AAV, suggesting an important role in MPO-AAV development |
(106) |
| Nephrotoxic serum nephritis | Effector Th cell | Murine/NTS | TIM3 is up-regulated in kidneys in NTS and exerts protective roles in the course of disease by suppressing the infiltration of inflammatory cells such as macrophages. | (102) |
IRI, ischemiareperfution injury; TLR-4, Toll-like receptor 4; NF-κB, nuclear factorκappa B; NLR-C4, Nod‐like receptor NLR family CARD domain‐containing protein 4; STZ, Streptozotocin; TNF-a, Tumor Necrosis Factor-α; eGFR, estimated glomerular filtration rate; anti-GBM, anti-glomerular basement membrane; MPO-AAV, myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis; NETs, neutrophil extracellular traps.