The crosstalk between parenchymal cells and macrophages: A keeper of tissue homeostasis

Non-parenchymal cells (NPCs) and parenchymal cells (PCs) collectively perform tissue-specific functions. PCs play significant roles and continuously adjust the intrinsic functions and metabolism of organs. Tissue-resident macrophages (TRMs) are crucial members of native NPCs in tissues and are essential for immune defense, tissue repair and development, and homeostasis maintenance. As a plastic-phenotypic and prevalent cluster of NPCs, TRMs dynamically assist PCs in functioning by producing cytokines, inflammatory and anti-inflammatory signals, growth factors, and proteolytic enzymes. Furthermore, the PCs of tissues modulate the functional activity and polarization of TRMs. Dysregulation of the PC-TRM crosstalk axis profoundly impacts many essential physiological functions, including synaptogenesis, gastrointestinal motility and secretion, cardiac pulsation, gas exchange, blood filtration, and metabolic homeostasis. This review focuses on the PC-TRM crosstalk in mammalian vital tissues, along with their interactions with tissue homeostasis maintenance and disorders. Thus, this review highlights the fundamental biological significance of the regulatory network of PC-TRM in tissue homeostasis.