Department of Dermatology, University of Illinois at Chicago, Chicago, IL, USA.
Department of Dermatology, University of Lübeck, Lübeck, Germany.
Exp Dermatol. 2021 Mar;30(3):304-318. doi: 10.1111/exd.14228. Epub 2020 Nov 19.
Dipeptidyl peptidase-4 (DPP4) is a multifunctional, transmembrane glycoprotein present on the cell surface of various tissues. It is present in multiple molecular forms including cell surface and soluble. The role of DPP4 and its inhibition in cutaneous dermatoses have been a recent point of investigation. DPP4 exerts a notable influence on T-cell biology, the induction of skin-specific lymphocytes, and the homeostasis between regulatory and effector T cells. Moreover, DPP4 interacts with a broad range of molecules, including adenosine deaminase, caveolin-1, CXCR4 receptor, M6P/insulin-like growth factor II-receptor and fibroblast activation protein-α, triggering downstream effects that modulate the immune response, cell adhesion and chemokine activity. DPP4 expression on melanocytes, keratinocytes and fibroblasts further alters cell function and, thus, has crucial implications in cutaneous pathology. As a result, DPP4 plays a significant role in bullous pemphigoid, T helper type 1-like reactions, cutaneous lymphoma, melanoma, wound healing and fibrotic disorders. This review illustrates the multifactorial role of DPP4 expression, regulation, and inhibition in cutaneous diseases.
二肽基肽酶-4(DPP4)是一种多功能的跨膜糖蛋白,存在于各种组织的细胞表面。它以多种分子形式存在,包括细胞表面和可溶性形式。DPP4 及其抑制在皮肤疾病中的作用是最近的研究重点。DPP4 对 T 细胞生物学、皮肤特异性淋巴细胞的诱导以及调节性和效应性 T 细胞之间的平衡有显著影响。此外,DPP4 与多种分子相互作用,包括腺苷脱氨酶、窖蛋白-1、CXCR4 受体、M6P/胰岛素样生长因子 II 受体和成纤维细胞激活蛋白-α,触发下游效应,调节免疫反应、细胞黏附和趋化因子活性。黑素细胞、角质形成细胞和成纤维细胞上的 DPP4 表达进一步改变细胞功能,因此在皮肤病理学中具有重要意义。因此,DPP4 在大疱性类天疱疮、Th1 样反应、皮肤淋巴瘤、黑色素瘤、伤口愈合和纤维化疾病中发挥重要作用。本综述说明了 DPP4 表达、调节和抑制在皮肤疾病中的多因素作用。