**3.1 Initiator of activation**

The most common initiator of KC activation is IL-1. In pathological conditions like psoriasis, KC process and release IL-1, allowing the surrounding cells to perceive it [82–84]. The released IL-1 serves as a paracrine signal to dermal endothelial cells to become activated, express selectins, and slow down the circulating lymphocytes [85, 86]. IL-1 also serves as a chemoattractant for lymphocytes, causing them to extravasate and migrate to the site of lesion [87]. Furthermore, IL-1 is an activator of dermal fibroblasts, enhancing their migration, proliferation, and production of dermal extracellular matrix components [88]. IL-1 is also an autocrine signal that activates KC. IL-1 causes them to proliferate, become migratory, and express an activation-specific set of genes [76]. Thus, IL-1 initiates KC activation not only by triggering additional signaling events, but also by inducing directly the synthesis of K6/K16 in epidermal KC, and thus changing the composition of their cytoskeleton.
