Keratinocytes as active regulators of cutaneous and mucosal immunity: a systematic review across inflammatory epithelial disorders

作者：Felix J Klimitz, Yizhuo Shen, Federico Repetto, Stav Brown, Leonard Knoedler, Christine J. Ko, Nebal Abu Hussein, William J. Crisler, Taylor Adams, Naftali Kaminski, Christine G. Lian, Gëorge F. Murphy, Henry C. Hsia, Bohdan Pomahač, Martin Kauke‐Navarro · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1694066 · 被引用次数：13 · 研究领域：Dermatology and Skin Diseases、Wound Healing and Treatments、Psoriasis: Treatment and Pathogenesis

Background: Keratinocytes are increasingly recognized as active regulators of immunity in both skin and mucosal inflammation. Although numerous studies have described their functions in individual conditions, no systematic synthesis has compiled keratinocyte-driven immune mechanisms across the major categories of epithelial injury disorders. We conducted a systematic review to fill this gap and identify both shared and disease-specific pathways that underlie keratinocyte-immune crosstalk in prototypical inflammatory dermatoses. Methods: because they are among the most common and clinically relevant inflammatory dermatoses, many with mucosal involvement, and together reflect diverse autoimmune, autoinflammatory, and alloimmune mechanisms. Key outcomes included keratinocyte signaling pathways, immune interactions, and tissue-specific responses. Results: Eighty-two studies met inclusion criteria: AD (n=49), psoriasis (n=11), LP (n=10), BP (n=3), LE (n=6), and GvHD (n=4). Keratinocytes were consistently implicated in cytokine production (e.g., IL-1β, IL-6, TNF-α, TSLP, IL-33), immune cell recruitment, and antigen presentation (via upregulation of MHC class II and costimulatory molecules such as ICAM-1 or B7). Shared activation pathways included NF-κB, JAK/STAT, and MAPK. Distinct immune profiles emerged across diseases: Th2-skewed responses in AD and BP, Th1/Th17 in psoriasis and LP, and type I interferons in LE and GvHD. Stress keratins (KRT6, KRT16, KRT17) were frequently upreg...