Excessive expression of TIM-3 on myeloid cells leads to inflammation in the lungs

Abstract

T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) has increasingly shown to exhibit unique characteristics and functions that differ according to the specific cell type and cell status. However, at present, little is known about the cell-specific properties of TIM-3 in pathophysiological conditions. Here, we show that TIM-3 on myeloid cells exerts essential roles in modulating inflammation and abnormality of lungs. We found that myeloid cell-specific TIM-3 knock-in (FSF-TIM3/LysM-Cre+) mice have a characteristic appearance of low body weight and short lifespans compared to WT mice. Interestingly, whole-body PET/CT analysis revealed that FSF-TIM3/LysM-Cre+ mice showed considerably high [18F]FDG uptake in the areas of lungs. Given that FSF-TIM3/LysM-Cre+ mice displayed abnormal features in lung areas, we next carefully examined the lungs. We observed that the lungs of FSF-TIM3/LysM-Cre+ mice were enlarged and histopathological examination showed features of disease-associated pathology compared to WT mice. Similar features were observed in a different myeloid cell-specific TIM-3 knock-in mouse (FSF-TIM3/Cx3cr1-Cre+). In addition, inflammation-related cytokines and the number of myeloid innate immune cells increased in the lungs of FSF-TIM3/LysM-Cre+ mice. Collectively, these findings suggest that TIM-3 is an important regulator of myeloid cells in the lungs and maybe a relevant therapeutic strategy against inflammation-associated lung disease.