# Cutaneous Dendritic Cells: Structure, Function and Immune Role

## TL;DR

This review explores the structure, function, and immune roles of cutaneous dendritic cells, highlighting their importance in skin immunity and disease.

## Contribution

The paper provides a first comprehensive review of cutaneous antigen-presenting cells in the context of the neuro-immune-cutaneous axis.

## Key findings

- Cutaneous APCs include diverse subsets like DC3, ASDCs, and mRegDCs with distinct roles in immune responses.
- Dynamic changes in APC composition occur in inflamed skin, influencing Th1 and Th17 immune circuits in diseases like psoriasis.
- Understanding APC diversity and interactions may lead to new biomarkers and therapies for skin diseases.

## Abstract

Cutaneous antigen-presenting cells (APCs), particularly dendritic cells (DCs) and Langerhans cells (LCs), are a diverse population of cells that play a vital role in immune surveillance by initiating and shaping skin immune responses. They link innate and adaptive immunity by presenting antigens, migrating, and activating T lymphocytes, thereby acting as orchestrators of tissue immunity. This review provides an updated overview of the morphofunctional diversity of cutaneous APCs, ranging from epidermal LCs and DCs, to dermal conventional DCs (DC1/DC2), plasmacytoid DCs (pDCs), including newly defined subsets such as DC3, Axl+Siglec-6+ DCs (ASDCs) and LAMP3+ mature regulatory DCs (mRegDCs). Dynamic differences in APC composition and function between homeostatic and inflamed skin are discussed, with particular emphasis on inflammatory and autoimmune conditions such as psoriasis, lupus erythematosus and chronic atopic dermatitis, in which distinct DC subsets contribute to Th1 and Th17 immune circuits. This review is the first skin-related approach that extensively discusses the cutaneous role of APCs in the neuro-immune-cutaneous axis, as well as their interactions with the local microenvironment. Ongoing controversies regarding the classification and stability of certain DC populations are discussed. A better understanding of the diversity, migration mechanisms and microenvironmental interactions of cutaneous APCs could lead to the identification of new biomarkers and therapeutic targets for inflammatory, autoimmune, and oncological skin diseases.