The role of Dipeptidyl Peptidase-4 in cutaneous disease

Exp Dermatol. 2021 Mar;30(3):304-318. doi: 10.1111/exd.14228. Epub 2020 Nov 19.

Abstract

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.

Keywords: Dipeptidyl Peptidase-4; autoimmunity; cancer; inflammatory skin diseases; wound healing.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Dermatitis, Atopic / genetics
  • Dermatitis, Atopic / immunology
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / immunology*
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects*
  • Humans
  • Immunity
  • Keratinocytes / metabolism
  • Leishmaniasis, Cutaneous / enzymology
  • Lymphocytes / metabolism
  • Lymphoma, T-Cell, Cutaneous / enzymology
  • Pemphigoid, Benign Mucous Membrane / chemically induced
  • Pemphigoid, Bullous / chemically induced
  • Psoriasis / enzymology
  • Skin Diseases / enzymology*
  • Skin Diseases / etiology*
  • Skin Neoplasms / enzymology
  • Wound Healing

Substances

  • Biomarkers, Tumor
  • Dipeptidyl-Peptidase IV Inhibitors
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4