TY - JOUR
T1 - Proteoglycans in Toll-like receptor responses and innate immunity
AU - Garantziotis, Stavros
AU - Savani, Rashmin C.
N1 - Publisher Copyright:
© 2022 the American Physiological Society.
PY - 2022/7
Y1 - 2022/7
N2 - The extracellular matrix (ECM) is an active and dynamic feature of tissues that not only provides gross structure but also plays key roles in cellular responses. The ever-changing microenvironment responds dynamically to cellular and external signals, and in turn influences cell fate, tissue development, and response to environmental injury or microbial invasion. It is therefore paramount to understand how the ECM components interact with each other, the environment and cells, and how they mediate their effects. Among the ECM components that have recently garnered increased attention, proteoglycans (PGs) deserve special note. Recent evidence strongly suggests that they play a crucial role both in health maintenance and disease development. In particular, proteoglycans dictate whether homeostasis or cell death will result from a given injury, by triggering and modulating activation of the innate immune system, via a conserved array of receptors that recognize exogenous (infectious) or endogenous (tissue damage) molecular patterns. Innate immune activation by proteoglycans has important implications for the understanding of cell-matrix interactions in health and disease. In this review, we will summarize the current state of knowledge of innate immune signaling by proteoglycans, discuss the implications, and explore future directions to define progress in this area of extracellular matrix biology.
AB - The extracellular matrix (ECM) is an active and dynamic feature of tissues that not only provides gross structure but also plays key roles in cellular responses. The ever-changing microenvironment responds dynamically to cellular and external signals, and in turn influences cell fate, tissue development, and response to environmental injury or microbial invasion. It is therefore paramount to understand how the ECM components interact with each other, the environment and cells, and how they mediate their effects. Among the ECM components that have recently garnered increased attention, proteoglycans (PGs) deserve special note. Recent evidence strongly suggests that they play a crucial role both in health maintenance and disease development. In particular, proteoglycans dictate whether homeostasis or cell death will result from a given injury, by triggering and modulating activation of the innate immune system, via a conserved array of receptors that recognize exogenous (infectious) or endogenous (tissue damage) molecular patterns. Innate immune activation by proteoglycans has important implications for the understanding of cell-matrix interactions in health and disease. In this review, we will summarize the current state of knowledge of innate immune signaling by proteoglycans, discuss the implications, and explore future directions to define progress in this area of extracellular matrix biology.
KW - Innate immunity
KW - Toll-like receptors
KW - proteoglycans
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U2 - 10.1152/ajpcell.00088.2022
DO - 10.1152/ajpcell.00088.2022
M3 - Review article
C2 - 35675639
AN - SCOPUS:85134426146
SN - 0363-6143
VL - 323
SP - C202-C214
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 1
ER -