Selective AhR knockout in langerin-expressing cells abates Langerhans cells and polarizes Th2/Tr1 in epicutaneous protein sensitization

Chien Hui Hong, Shang Hung Lin, Björn E. Clausen, Chih Hung Lee*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

10 Scopus citations

Abstract

The aryl hydrocarbon receptor (AhR) represents an environmental sensor regulating immune responses. In the skin, AhR is expressed in several cell types, including keratinocytes, epidermal Langerhans cells (LC), and dermal dendritic cells (DC). The mechanisms how AhR activates or inhibits cutaneous immune responses remain controversial, owing to differences in the cell-specific functions of AhR and the different activating ligands. Therefore, we sought to investigate the role of AhR in LC and langerin+ and negative DC in the skin. To this aim, we generated Langerin-specific and CD11c-specific knockout (/) mice lacking AhR, respectively, in LC and Langerin+ dermal DC and in all CD11c+ cells. These were then tested in an epicutaneous protein (ovalbumin, Ova) sensitization model. Immunofluorescence microscopy and flow cytometry revealed that Langerin-AhR/ but not CD11cAhR/ mice harbored a decreased number of LC with fewer and stunted dendrites in the epidermis as well as a decreased number of LC in skin-draining lymph nodes (LN). Moreover, in the absence of AhR, we detected an enhanced T helper type-2 (Th2) [increased interleukin 5 (IL-5) and interleukin 13 (IL-13)] and T regulatory type-1 (Tr1) (IL-10) response when LN cells were challenged with Ova in vitro, though the number of regulatory T cells (Treg) in the LN remained comparable. Langerin-AhR/ mice also exhibited increased blood levels of Ova-specific immunoglobulin E (IgE). In conclusion, deletion of AhR in langerin-expressing cells diminishes the number and activation of LC, while enhancing Th2 and Tr1 responses upon epicutaneous protein sensitization.

Original languageEnglish
Pages (from-to)12980-12990
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number23
DOIs
StatePublished - 09 06 2020

Bibliographical note

Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.

Keywords

  • Aryl hydrocarbon receptor
  • Epicutaneous protein sensitization
  • Langerhans cells
  • Th2
  • Tr1

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