1. Smad4 deficiency inhibits lung metastases through enhancing phagocytosis of lung interstitial macrophages.
- Author
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Song Y, Gu D, Gao N, Sa H, Wang R, Fang L, and Yuan Z
- Subjects
- Animals, Mice, Cell Line, Tumor, Lung pathology, Lung immunology, Lung metabolism, Macrophages immunology, Macrophages metabolism, Macrophages, Alveolar metabolism, Macrophages, Alveolar immunology, Macrophages, Alveolar pathology, Mice, Inbred C57BL, Mice, Knockout, Lung Neoplasms secondary, Lung Neoplasms immunology, Lung Neoplasms pathology, Lung Neoplasms genetics, Melanoma, Experimental pathology, Melanoma, Experimental immunology, Phagocytosis genetics, Smad4 Protein deficiency, Smad4 Protein genetics, Smad4 Protein metabolism
- Abstract
Smad4, a critical mediator of TGF-β signaling, plays a pivotal role in regulating various cellular functions, including immune responses. In this study, we investigated the impact of Smad4 knockout specifically in macrophages on anti-tumor immunity, focusing on lung metastasis of B16 melanoma cells. Using a mouse model with Smad4 knockout in macrophages established via Lyz2-cre mice and Smad4 flox/flox mice, we demonstrated a significant inhibition of B16 metastasis in the lungs. Interestingly, the inhibition of tumor growth was found to be independent of adaptive immunity, as no significant changes were observed in the numbers or activities of T cells, B cells, or NK cells. Instead, Smad4 knockout led to the emergence of an MCHII
low CD206high subset of lung interstitial macrophages, characterized by enhanced phagocytosis function. Our findings highlight the crucial role of Smad4 in modulating the innate immune response against tumors and provide insights into potential therapeutic strategies targeting lung interstitial macrophages to enhance anti-tumor immunity., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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