Abstract
During the inflammatory response, immune cells egress from the circulation and follow a chemotactic and haptotactic gradient within the tissue, interacting with matrix components in the stroma and with parenchymal cells, which guide them towards the sites of inflammation. Polarized epithelial cells compartmentalize tissue cavities and are often exposed to inflammatory challenges such as toxics or infections in non-lymphoid tissues. Apicobasal polarity is critical to the specialized functions of these epithelia. Indeed, a common feature of epithelial dysfunction is the loss of polarity. Here we review evidence showing that apicobasal polarity regulates the inflammatory response: various polarized epithelia asymmetrically secrete chemotactic mediators and polarize adhesion receptors that dictate the route of leukocyte migration within the parenchyma. We also discuss recent findings showing that the loss of apicobasal polarity increases leukocyte adhesion to epithelial cells and the consequences that this could have for the inflammatory response towards damaged, infected or transformed epithelial cells.
Highlights
Leukocyte recruitment into the inflamed parenchyma requires successive interactions with cellular and stromal barriers that establish mechanical, chemotactic and haptotactic gradients to guide immune cells towards the inflammatory focus
Few studies have addressed the contribution of abluminal endothelial surfaces, the basement membrane and the pericyte barriers to leukocyte trafficking into the tissue, but the most recent reports suggest a pro-active role for pericytes in controlling leukocyte navigation into the parenchyma through the intercellular adhesion molecule-1 (ICAM-1), the counter-receptor of β2-integrins, which is expressed in pericytes at levels comparable to those in inflamed endothelial cells [10,11,12]
This suggests that interactions with ICAM-1 probably follow the leukocyte crossing through junctional adhesion molecules (JAMs) and CD47 basolateral surfaces and mediate the return of immune cells from the epithelial lumen towards the parenchyma
Summary
Leukocyte recruitment into the inflamed parenchyma requires successive interactions with cellular and stromal barriers that establish mechanical, chemotactic and haptotactic gradients to guide immune cells towards the inflammatory focus. Few studies have addressed the contribution of abluminal endothelial surfaces, the basement membrane and the pericyte barriers to leukocyte trafficking into the tissue, but the most recent reports suggest a pro-active role for pericytes in controlling leukocyte navigation into the parenchyma through the intercellular adhesion molecule-1 (ICAM-1), the counter-receptor of β2-integrins, which is expressed in pericytes at levels comparable to those in inflamed endothelial cells [10,11,12] This interaction occurs mainly in postcapillary venules, where myeloid leukocytes egress through regions between pericytes that have low density of matrix proteins [13]. Many cell types orchestrate this program either directly, by interacting with leukocytes, or indirectly, by secreting mediators and extracellular matrix components
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
