Lin Tzu-Kai, Man Mao-Qiang, Abuabara Katrina, Wakefield Joan S, Sheu Hamm-Ming, Tsai Jui-Chen, Lee Chih-Hung, Elias Peter M
Department of Dermatology Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan.
School of Medicine Tzu Chi University Hualien Taiwan.
Evol Appl. 2019 Sep 24;12(10):1960-1970. doi: 10.1111/eva.12858. eCollection 2019 Dec.
Pigmentation evolved in ancestral humans to protect against toxic, ultraviolet B irradiation, but the question remains: "what is being protected?" Because humans with dark pigmentation display a suite of superior epidermal functions in comparison with their more lightly pigmented counterparts, we hypothesized and provided evidence that dark pigmentation evolved in Africa to support cutaneous function. Because our prior clinical studies also showed that a restoration of a competent barrier dampens cutaneous inflammation, we hypothesized that resistance to inflammation could have provided pigmented hominins with yet another, important evolutionary benefit. We addressed this issue here in two closely related strains of hairless mice, endowed with either moderate (Skh2/J) or absent (Skh1) pigmentation. In these models, we showed that (a) pigmented mice display a markedly reduced propensity to develop inflammation after challenges with either a topical irritant or allergen in comparison with their nonpigmented counterparts; (b) visible and histologic evidence of inflammation was paralleled by reduced levels of pro-inflammatory cytokines (i.e., IL-1α and INFα); (c) because depigmentation of Skh2/J mouse skin enhanced both visible inflammation and pro-inflammatory cytokine levels after comparable pro-inflammatory challenges, the reduced propensity to develop inflammation was directly linked to the presence of pigmentation; and (d) furthermore, in accordance with our prior work showing that pigment production endows benefits by reducing the surface pH of skin, acidification of albino (Skh1) mouse skin also protected against inflammation, and equalized cytokine levels to those found in pigmented skin. In summary, pigmentation yields a reduced propensity to develop inflammation, consistent with our hypothesis that dark pigmentation evolved in ancestral humans to provide a suite of barrier-linked benefits that now include resistance to inflammation.
色素沉着在人类祖先中进化出来是为了抵御有毒的紫外线B辐射，但问题仍然存在：“被保护的是什么？” 因为与色素较浅的人相比，色素沉着较深的人表现出一系列更优越的表皮功能，我们提出并提供了证据，证明深色色素沉着在非洲进化是为了支持皮肤功能。由于我们之前的临床研究还表明，恢复正常的屏障功能可以减轻皮肤炎症，我们推测对炎症的抵抗力可能为有色素的人类提供了另一个重要的进化优势。我们在两种密切相关的无毛小鼠品系中解决了这个问题，一种具有中等色素沉着（Skh2/J），另一种没有色素沉着（Skh1）。在这些模型中，我们发现：（a）与无色素的小鼠相比，有色素的小鼠在受到局部刺激物或过敏原刺激后发生炎症的倾向明显降低；（b）炎症的可见和组织学证据与促炎细胞因子（即IL-1α和INFα）水平的降低相平行；（c）由于Skh2/J小鼠皮肤的色素脱失在可比的促炎刺激后增强了可见炎症和促炎细胞因子水平，炎症发生倾向的降低与色素沉着的存在直接相关；（d）此外，根据我们之前的研究表明色素生成通过降低皮肤表面pH值带来益处，白化（Skh1）小鼠皮肤的酸化也能预防炎症，并使细胞因子水平与有色素皮肤中的水平相等。总之，色素沉着使发生炎症的倾向降低，这与我们的假设一致，即人类祖先中的深色色素沉着进化出来是为了提供一系列与屏障相关的益处，现在包括对炎症的抵抗力。
