Journal Article

Fate mapping analysis reveals a novel murine dermal migratory Langerhans-like cell population

Liang, Tingbo, Sung, Yang Ho, Chen, Qi, Mayer, Johannes, Zhang, Junlei, Bai, Xueli, Sheng, Jianpeng, Ronchese, Franca, Wang, Lin, Goh, Wilson Wen Bin, Ruedl, Christiane, Wu, Xiaoting, Dong, Yu Wen

2021

Overview

Dendritic cells residing in the skin represent a large family of antigen-presenting cells, ranging from long-lived Langerhans cells (LC) in the epidermis to various distinct classical dendritic cell subsets in the dermis. Through genetic fate mapping analysis and single-cell RNA-sequencing, we have identified a novel separate population of LC-independent CD207 + CD326 + LC like cells in the dermis that homed at a slow rate to the lymph nodes (LNs). These LC like cells are long-lived and radio-resistant but, unlike LCs, they are gradually replenished by bone marrow-derived precursors under steady state. LC like cells together with cDC1s are the main migratory CD207 + CD326 + cell fractions present in the LN and not, as currently assumed, LCs, which are barely detectable, if at all. Cutaneous tolerance to haptens depends on LC like cells, whereas LCs suppress effector CD8 + T-cell functions and inflammation locally in the skin during contact hypersensitivity. These findings bring new insights into the dynamism of cutaneous dendritic cells and their function opening novel avenues in the development of treatments to cure inflammatory skin disorders. Our immune cells are constantly on guard to defend and protect us against invading pathogens, such as bacteria and viruses. Specialized immune cells, known as antigen-presenting cells, or APCs, have a key role in this process. They engulf invaders, chew them up, and travel to the closest local lymph node to stimulate other immune cells with small fragments of these pathogens. This ramps up the immune response to control infection and disease. APCs are a large and diverse family of immune cells, which includes dendritic cells and macrophages. Some APCs work as mobile surveillance units, travelling around the body to find new threats. Others embed themselves in particular organs and tissues, such as the skin, to provide local, on-the-spot surveillance. Langerhans cells are one of the main types of APC in the skin and are found in the thin outer layer of the epidermis. While it is commonly believed that Langerhans cells can move from the epidermis to the skin-draining lymph nodes, some seemingly contradictory evidence exists to suggest that this may not be the case. Now, Sheng et al. have investigated this issue by tracking APCs, including Langerhans cells, in the skin of mice. A powerful genetic cell labelling technique allowed them to track the movement of immune cells inside a living mouse. Sheng et al. found that majority of 'real' Langerhans cells did not leave the skin. Yet, a second lookalike cell that shared many of the same features of a Langerhans cell was found in the dermal layer of skin, and this cell could travel to local lymph nodes. Both the original and lookalike cells had distinct and separate roles in the skin. This research, which has uncovered a new type of Langerhans-like immune cell in the skin, may be extremely useful for developing new targeted therapies to boost immune responses during infection; or to suppress inappropriate immune activation that can lead to autoimmune diseases, such as psoriasis.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Antigen presentation / Antigen-presenting cells / Bone marrow / CD8 antigen / Cell fate / Cell migration / Contact dermatitis / dendritic cell / Dendritic cells / Dermis / Effector cells / Epidermis / Fate maps / Flow cytometry / Gene mapping / Genetic analysis / Haptens / Hypersensitivity / Immunological tolerance / Immunology and Inflammation / Langerhans cell / Langerhans cells / lymph node / Lymph nodes / Lymphatic system / Lymphocytes T / Osteoprogenitor cells / Population / skin / Skin diseases