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Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental

Xiaochun Liu1, Ronghui Zhu2, Yang Luo1

  • 1Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China.

Immunity
|September 11, 2021
PubMed

Insights

Researchers discovered distinct human Langerhans cell (LC) subsets (LC1 and LC2) with unique functions in skin immunity. These subsets, identified using advanced single-cell analysis, have different developmental paths and roles in immune responses.

Area of Science:

  • Immunology
  • Dermatology
  • Cell Biology

Background:

  • Langerhans cells (LCs) are crucial for skin homeostasis.
  • The heterogeneity of LC populations has been long recognized but not fully elucidated.

Purpose of the Study:

  • To identify and characterize distinct subsets of human Langerhans cells.
  • To understand the developmental regulation and functional differences between these subsets.

Main Methods:

  • Single-cell RNA sequencing
  • Mass cytometry
  • Analysis of LCs from human skin epidermis and CD34+ hemopoietic stem cells (HSC-LCs) differentiation.

Main Results:

  • Identified two steady-state (LC1, LC2) and two activated human LC subsets.
  • EGR1 and Notch signaling pathways regulate LC1/LC2 differentiation.
  • LC1 function in innate immunity and antigen processing; LC2 resemble monocytes/myeloid dendritic cells, involved in immune responses.
  • LC1 are stable in inflammation; LC2 are activated by inflammation and express immunosuppressive molecules.

Conclusions:

  • Distinct human LC subsets possess unique functional properties and developmental trajectories.
  • Understanding LC subset heterogeneity is key to deciphering skin immune regulation.

Keywords:
Langerhans cellsdifferentiationfunctionheterogeneityhumanmass cytometryphenotypesingle-cell RNA sequencing

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