Macrophages can be characterized as a very multifunctional cell type with a spectrum of phenotypes and functions being observed spatially and temporally in various disease states. Ample studies have now demonstrated a possible causal link between macrophage activation and the development of autoimmune disorders. How these cells may be contributing to the adaptive immune response and potentially perpetuating the progression of neurodegenerative diseases and neural injuries is not fully understood. Within this review, we hope to illustrate the role that macrophages and microglia play as initiators of adaptive immune response in various CNS diseases by offering evidence of: (1) the types of immune responses and the processes of antigen presentation in each disease, (2) receptors involved in macrophage/microglial phagocytosis of disease-related cell debris or molecules, and, finally, (3) the implications of macrophages/microglia on the pathogenesis of the diseases.
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Biophysical regulation of macrophages in health and disease
Macrophages perform critical functions for homeostasis and immune defense in tissues throughout the body. These innate immune cells are capable of recognizing and clearing dead cells and pathogens, and orchestrating inflammatory and healing processes that occur in response to injury. In addition, macrophages are involved in the progression of many inflammatory diseases including cardiovascular disease, fibrosis, and cancer. Although it has long been known that macrophages respond dynamically to biochemical signals in their microenvironment, the role of biophysical cues has only recently emerged. Furthermore, many diseases that involve macrophages are also characterized by changes to the tissue biophysical environment. This review will discuss current knowledge about the effects of biophysical cues including matrix stiffness, material topography, and applied mechanical forces, on macrophage behavior. We will also describe the role of molecules that are known to be important for mechanotransduction, including adhesion molecules, ion channels, as well as nuclear mediators such as transcription factors, scaffolding proteins, and epigenetic regulators. Together, this review will illustrate a developing role of biophysical cues in macrophage biology, and also speculate upon molecular targets that may potentially be exploited therapeutically to treat disease.
more » « less- Award ID(s):
- 1763272
- NSF-PAR ID:
- 10394042
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Journal of Leukocyte Biology
- Volume:
- 106
- Issue:
- 2
- ISSN:
- 0741-5400
- Page Range / eLocation ID:
- p. 283-299
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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