Cytoskeletal organization alters both epithelial barrier function and immune responses

Abstract

Changing microtubule polymerization in primary airway epithelial cells alters paracellular permeability. Treatment with nocodazole, which causes microtubule depolymerization, we see a decrease in paracellular permeability. In addition, when we knockdown AQP5, a membrane water channel, we see a decrease in paracellular permeability along with destabilization of microtubules. Our data suggests that AQP5 has a novel role as a microtubule stabilizing protein. Regulation of AQP5 modulates microtubule organization and dynamically regulates barrier function. Furthermore, our data shows that these changes in paracellular permeability regulate polarized epithelial responses to known stimuli such as EGF, IFNg and Substance P, as well as epithelial ligand expression, which mediates one mechanism by which epithelial cells interact with immune cells. Knocking down AQP5 in primary airway epithelial cells significantly increases the expression of the co‐repressor molecule, B7‐H1, which functions to decrease the immune response. Similar findings occur with treatment of the cells with microtubule destabilizing agents. These data suggest that alterations in cytoskeletal organization effect both how an epithelial cell interacts with a neighboring epithelial cell, as well as how it interacts with the immune system.