Molecular regulation of TLR signaling in health and disease: mechano-regulation of macrophages and TLR signaling

Immune cells continuously patrol the body to rapidly detect and respond to endogenous and exogenous insults. Compared with other cell types, immune cells are extremely motile, able to undergo dramatic morphological changes during tissue transit, and capable of dynamic cell–cell interactions for Ag presentation and transmigration under static and circulatory flow conditions. A direct consequence of their motility is that immune cells encounter microenvironments that vary tremendously in terms of both physical and biochemical properties (Table 1). For over 40 yr, immunologists have studied biochemical signals, such as cytokines, to understand intercellular communication networks. Initial work in the 1970s and the cloning of IL-1 in 1984 paved the way for the subsequent development of numerous knockout mouse lines deficient in cytokines or their receptors that advanced our detailed understanding of these biochemical networks.1 For at least a decade, we have also known that the physical microenvironment can drive differentiation of mesenchymal stem cells,2 yet these studies on biophysical signaling have only recently been described for immune cells, and our understanding of the mechanisms and molecular players in immune mechanobiology are not well described. Table 1. Characteristics of tissue microenvironments that change and modulate immune cell function.