Schäbitz A, Eyerich K, Garzorz-Stark N
From the, Division of Dermatology and Venereology, Department of Medicine Solna, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Dermatology and Venereology, Unit of Dermatology, Karolinska University Hospital, Stockholm, Sweden.
J Intern Med. 2021 Jul;290(1):27-39. doi: 10.1111/joim.13235. Epub 2021 Jan 11.
Characterization of the complex interplay between cytokines, chemokines and microorganisms has led to a better understanding of the pathogenesis of both psoriasis and AD and resulted in new therapeutics targeting distinct immune responses. Psoriasis and AD share many characteristics: they are highly prevalent, chronic, cause primarily skin inflammation, but are associated with comorbidities, and come with a devastating quality of life due to itch and stigmatization. However, the pathogenesis of psoriasis and AD is opposing - psoriasis is dominated by a Th17 immune response that causes neutrophil migration, induction of innate immunity and exaggerated epithelial metabolism. Leading cytokines of this Th17 immune response are IL-17A and F, IL-22 and TNF-a. AD is characterized by Th2 immunity characterized by the signature cytokines IL-4 and IL-13 leading to an impaired epidermal barrier, dampened innate immunity and eosinophil migration. This review compares genetics, microbiome and T-cell infiltrate and resulting epithelial response in psoriasis and AD. Whilst the antagonistic course of psoriasis and AD is confirmed by response to specific biologics targeting the key cytokines of inflammation in psoriasis and AD, respectively, clinically overlapping phenotypes are challenging in our daily clinical practice. We conclude this review by summarizing what is known about these mixed phenotypes and how the identification of clinically relevant endotypes and molecular-driven decision-making is the next step in the field of dermato-immunology.
细胞因子、趋化因子与微生物之间复杂相互作用的特征分析，使人们对银屑病和特应性皮炎的发病机制有了更深入的了解，并催生出针对不同免疫反应的新疗法。银屑病和特应性皮炎有许多共同特征：它们非常常见、呈慢性病程，主要引起皮肤炎症，但与合并症有关，且由于瘙痒和污名化而严重影响生活质量。然而，银屑病和特应性皮炎的发病机制相反——银屑病以Th17免疫反应为主导，该反应会导致中性粒细胞迁移、诱导先天免疫和上皮代谢亢进。这种Th17免疫反应的主要细胞因子是IL-17A和F、IL-22和TNF-α。特应性皮炎的特征是Th2免疫，其标志性细胞因子为IL-4和IL-13，会导致表皮屏障受损、先天免疫减弱和嗜酸性粒细胞迁移。本综述比较了银屑病和特应性皮炎的遗传学、微生物群、T细胞浸润以及由此产生的上皮反应。虽然分别针对银屑病和特应性皮炎炎症关键细胞因子的特异性生物制剂的反应证实了银屑病和特应性皮炎的拮抗过程，但在我们的日常临床实践中，临床重叠的表型具有挑战性。我们通过总结关于这些混合表型的已知信息以及如何识别临床相关的内型和分子驱动的决策是皮肤免疫学领域的下一步，来结束本综述。
