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

eLife

Johannes Mayer¹  Franca Ronchese¹  Yang Ho Sung²  Qi Chen²  Xiaoting Wu²  Wilson Wen Bin Goh²  Christiane Ruedl²  Yu Wen Dong²  Xueli Bai³  Lin Wang³  Junlei Zhang³  Tingbo Liang³  Jianpeng Sheng⁴ 

[1] Malaghan Institute of Medical Research, Wellington, New Zealand;Nanyang Technological University, School of Biological Sciences, Singapore, Singapore;Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;Nanyang Technological University, School of Biological Sciences, Singapore, Singapore;

关键词: skin;    cell migration;    dermis;    lymph node;    dendritic cell;    Langerhans cell;    Mouse;   

DOI  :  10.7554/eLife.65412

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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+ LClike cells in the dermis that homed at a slow rate to the lymph nodes (LNs). These LClike cells are long-lived and radio-resistant but, unlike LCs, they are gradually replenished by bone marrow-derived precursors under steady state. LClike 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 LClike 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.

【 授权许可】

CC BY