Integrins are heterodimeric trans-membrane receptors that connect the cellular cytoskeleton to the extracellular matrix and play a vital role in cellular processes such as proliferation, differentiation, migration and adhesion. The loss of the integrin 1 subunit from the skin epidermis results neonatal lethality due to a failure in organization of the epithelial basement membrane and subsequent loss of adhesion between the epidermis and the underlying dermis. These phenotypes underscore the importance of Integrins in cell adhesion, migration and stem cell maintenance, all of which are being further analyzed in the lab.
The integrin KO mice display a strong inflammatory and wound response that is associated with the recruitment of immune cells from both the innate and adaptive immune system. Of particular importance is the fact that that this immune response is elicited during embryonic development, in the presence of an intact barrier and at a time when there are no extrinsic wounds and no skin microbiome that may facilitate this process. We have extensively characterized this immune response and the role it plays in the organization/remodeling of the ECM. The integrin KO mouse thus offers and excellent model system to address the nexus between the wound and immune response and the signaling processes that may be involved in the process sterile inflammation.