Department of Dermatology, Medical University of Graz, Graz, Styria, Austria.
Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Exp Dermatol. 2021 Jun;30(6):841-846. doi: 10.1111/exd.14310. Epub 2021 Feb 25.
Topical dithranol is effective in autoimmune conditions like alopecia areata, inducing hair regrowth in a high percentage of cases. Exact mechanisms of dithranol in alopecia areata, with seemingly healthy epidermis besides altered hair follicles, are not well understood. To better understand dithranol's mechanisms on healthy skin, we analysed its effect on normal murine as well as xenografted human skin. We found a strong increase in mRNA expression of anti-microbial peptides (AMPs) (eg Lcn2, Defb1, Defb3, S100a8, S100a9), keratinocyte differentiation markers (eg Serpinb3a, Flg, Krt16, Lce3e) and inflammatory cytokines (eg Il1b and Il17) in healthy murine skin. This effect was paralleled by inflammation and disturbed skin barrier, as well as an injury response resulting in epidermal hyperproliferation, as observed in murine and xenografted adult human skin. This contact response and disturbed barrier induced by dithranol might lead via a vicious loop between AMPs such as S100a8/a9 (that led to skin swelling itself after topical application) and cytokines such as IL-1β to an immune suppressive environment in the skin. A better understanding of the skin's physiologic response to dithranol may open up new avenues for the establishment of novel therapeutics (including AMP-related/interfering molecules) for certain skin conditions, such as alopecia areata.
局部地蒽酚对斑秃等自身免疫性疾病有效，能使大多数病例的毛发再生。除了改变的毛囊外，地蒽酚在斑秃中的确切作用机制尚不清楚。为了更好地了解地蒽酚对健康皮肤的作用机制，我们分析了它对正常小鼠皮肤和异种移植的人皮肤的影响。我们发现正常小鼠皮肤的抗菌肽（AMP）（如 Lcn2、Defb1、Defb3、S100a8、S100a9）、角蛋白细胞分化标志物（如 Serpinb3a、Flg、Krt16、Lce3e）和炎症细胞因子（如 Il1b 和 Il17）的 mRNA 表达显著增加。这种效应伴随着炎症和皮肤屏障紊乱，以及表皮过度增殖的损伤反应，在小鼠和异种移植的成年人类皮肤中均观察到这种现象。地蒽酚引起的这种接触反应和屏障紊乱可能会通过 AMP（如 S100a8/a9，其在局部应用后会导致皮肤肿胀）和细胞因子（如 IL-1β）之间的恶性循环导致皮肤中的免疫抑制环境。更好地了解皮肤对地蒽酚的生理反应可能会为某些皮肤疾病（如斑秃）开辟新的治疗途径（包括与 AMP 相关/干扰的分子）。
