Traditional remedies for common disorders have been known for centuries, but insight into their mechanism of action is often limited. In this issue of the JCI, Joost Schalkwijk’s research group at the Radboud University Nijmegen Medical Centre in The Netherlands advances our understanding of why topical coal tar is an effective treatment for atopic dermatitis (AD), both rationalizing the use of this traditional medicine, and providing the scientific basis for new therapeutic approaches.
(A) Schematic of the epidermis showing the expression of filaggrin (and related proteins involved in the biogenesis of the skin barrier) within the granular cell layers that underlie the dead, terminally differentiated squames of the stratum corneum where the skin’s barrier function mainly resides. An intact skin barrier prevents water loss as well as entry of foreign material into the body. (B) In many patients with AD, there is either an inherited defect in barrier formation (e.g., due to filaggrin deficiency) and/or indirect repression of skin barrier genes (e.g., by the action of Th2 cytokines). The defective barrier allows entry of foreign substances, which leads to an inflammatory response where Th2 cytokines are especially important. These cytokines further repress skin barrier formation, thereby completing a negative feedback loop. (C) Schalkwijk’s group show here that coal tar acts via the AHR, which has two beneficial effects: (a) increasing epidermal differentiation and upregulating the expression of key barrier proteins such as filaggrin, and (b) suppressing the Th2 cytokine response. Thus, coal tar is able to break the mechanistic cycle in AD.