120 Identification of keratinocyte mitogens: implications for hyperproliferation in psoriasis and atopic dermatitis

Psoriasis and atopic dermatitis (AD) are chronic inflammatory skin diseases characterized by keratinocyte hyperproliferation epidermal acanthosis (hyperplasia). The milieu of disease- associated cytokines soluble factors is considered a mitogenic factor, however, pinpointing the exact mitogens in this complex microenvironment challenging. We employed organotypic human equivalents (HEEs), faithfully mimicking native proliferation stratification, to evaluate proliferative effects broad panel (literature-based) potential mitogens. growth factor molecule (KGF), T-helper 2 (Th2) interleukin-4 (IL-4) IL-13 psoriasis-associated cytokine IL-17A caused hyperplasia through doubling number proliferating keratinocytes. In contrast, IFN-g lowered proliferation, while IL-6, IL-20, IL-22 oncostatin M (OSM), induced not but hypertrophy. Th2-cytokine mediated was JAK/STAT3 dependent, KGF MEK/ERK-dependent proliferation. This discovery that key regulators AD psoriasis direct only adds evidence their crucial role pathophysiological processes also highlights an additional therapeutic pillar for mode action targeting biologicals (e.g. dupilumab) or small drugs tofacitinib) normalization turnover within compartment.