1. TIM-3 on myeloid cells promotes pulmonary inflammation through increased production of galectin-3.
- Author
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Kim KS, Lee C, Kim HS, Gu SJ, Yoon HJ, Won SB, Lee H, Lee YS, Kim SS, Kane LP, and Park EJ
- Subjects
- Animals, Mice, Mice, Knockout, Mice, Inbred C57BL, Galectins metabolism, Galectins genetics, Lung pathology, Lung metabolism, Hepatitis A Virus Cellular Receptor 2 metabolism, Hepatitis A Virus Cellular Receptor 2 genetics, Galectin 3 metabolism, Galectin 3 genetics, Myeloid Cells metabolism, Pneumonia metabolism, Pneumonia pathology, Pneumonia genetics
- Abstract
T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) exhibits unique, cell type- and context-dependent characteristics and functions. Here, we report that TIM-3 on myeloid cells plays essential roles in modulating lung inflammation. We found that myeloid cell-specific TIM-3 knock-in (FSF-TIM3/LysM-Cre
+ ) mice have lower body weight and shorter lifespan than WT mice. Intriguingly, the lungs of FSF-TIM3/LysM-Cre+ mice display excessive inflammation and features of disease-associated pathology. We further revealed that galectin-3 levels are notably elevated in TIM-3-overexpressing lung-derived myeloid cells. Furthermore, both TIM-3 blockade and GB1107, a galectin-3 inhibitor, ameliorated lung inflammation in FSF-TIM3/LysM-Cre+/- mice. Using an LPS-induced lung inflammation model with myeloid cell-specific TIM-3 knock-out mice, we demonstrated the association of TIM-3 with both lung inflammation and galectin-3. Collectively, our findings suggest that myeloid TIM-3 is an important regulator in the lungs and that modulation of TIM-3 and galectin-3 could offer therapeutic benefits for inflammation-associated lung diseases., (© 2024. The Author(s).)- Published
- 2024
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