Alarmins/stressorins and immune dysregulation in intractable skin disorders.

Unlike other barrier epithelia of internal organs, the stratified squamous epithelium of the skin is always exposed to the external environment. However, the robust barrier structure and function of the skin are highly resistant against external insults so as to not easily allow foreign invasions. Upon sensing danger signals, the innate immunity system is promptly activated. This process is mediated by alarmins, which are released passively from damaged cells. Nuclear alarmins or stressorins are actively released from intact cells in response to various cellular stresses. Alarmins/stressorins are deeply involved in the disease processes of chronic skin disorders of an unknown cause, such as rosacea, psoriasis, and atopic dermatitis. Furthermore, alarmins/stressorins are also induced in the congenital skin disorders of ichthyosis and keratoderma due to defective keratinization. Studies on alarmin activation and its downstream pathways may help develop novel therapeutic agents for intractable skin disorders.