Distinguished role of MerTk and Axl receptors-mediated efferocytosis in alveolar macrophages on pulmonary mucosal regulation
JOURNAL OF IMMUNOLOGY(2023)
摘要
Abstract Efferocytosis is paramount to regulating homeostasis and inflammation. The TAM receptor family (Tyro3, Axl and MerTk) mediates efferocytosis and simultaneously inhibits pro-inflammatory pathways. Here we investigated how MerTk and Axl regulate pulmonary mucosa homeostasis and inflammation, using silicosis as a study model. During homeostasis, lung cells and alveolar macrophages (AMs) from wild-type (WT) mice showed high expression of Axl, MerTk, and Gas6. Although we have found increased numbers of total airway cells, lower levels of TGF-b and IL-10, and higher levels of nitric oxide in the BALFs from both Axl −/−and MerTk −/−compared to WT mice, enhanced numbers of lung total cells, higher numbers of AMs, monocytes, and neutrophils were found in BALFs and lungs of MerTk −/−compared to Axl −/−or WT mice. We also found increased expression of CXCL1, CXCL2, TNF-a, and IL-6, and enhanced numbers of MHCII +AMs in the lungs of MerTk −/−compared to Axl −/−or WT mice. Furthermore, AMs from Axl −/−mice upregulated the expression of MerTk receptor. During silicosis, we found decreased pulmonary function, increased levels of TGF-b and CXCL1, as well as increased number of AMs and neutrophils in silicotic (SIL)-Axl mice compared to the SIL-MerTk or SIL-WT groups. In addition, SIL-Axl showed a reduced number of CD206 +AMs and an enhanced number of apoptotic, late apoptotic, and necrotic AMs compared to SIL-MerTk or SIL-WT groups. Finally, we found that both SIL-WT and SIL-MerTk upregulated mRNA levels for Axl compared to its PBS groups. Collectively, our data suggest that MerTk and Axl receptor-mediated efferocytosis are dedicated to regulating homeostasis and controlling inflammation in the lungs, respectively. CNPq, CAPES and FAPERJ
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关键词
alveolar macrophages,pulmonary mucosal regulation,efferocytosis,receptors-mediated
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