PMID- 32461368
OWN - NLM
STAT- MEDLINE
DCOM- 20200821
LR  - 20201127
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 117
IP  - 23
DP  - 2020 Jun 9
TI  - Selective AhR knockout in langerin-expressing cells abates Langerhans cells and 
      polarizes Th2/Tr1 in epicutaneous protein sensitization.
PG  - 12980-12990
LID - 10.1073/pnas.1917479117 [doi]
AB  - 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 CD11c-AhR(-/-) 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.
FAU - Hong, Chien-Hui
AU  - Hong CH
AUID- ORCID: 0000-0002-5118-620X
AD  - Department of Dermatology, Faculty of Medicine, National Yang-Ming University, 
      Taipei 11221, Taiwan.
AD  - Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, 
      Taiwan.
FAU - Lin, Shang-Hung
AU  - Lin SH
AD  - Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 
      83301, Taiwan.
AD  - Department of Dermatology, Chang Gung University College of Medicine, Taoyuan 
      33302, Taiwan.
FAU - Clausen, Bjorn E
AU  - Clausen BE
AUID- ORCID: 0000-0002-2484-7842
AD  - Institute for Molecular Medicine, University Medical Center of the Johannes 
      Gutenberg-University, Mainz 55131, Germany.
FAU - Lee, Chih-Hung
AU  - Lee CH
AUID- ORCID: 0000-0001-9804-3874
AD  - Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 
      83301, Taiwan; dermlee@gmail.com.
AD  - Department of Dermatology, Chang Gung University College of Medicine, Taoyuan 
      33302, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200527
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Ahr protein, mouse)
RN  - 0 (Antigens, Surface)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Cd207 protein, mouse)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Administration, Cutaneous
MH  - Animals
MH  - Antigens, Surface/metabolism
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism
MH  - Epidermis/immunology/metabolism
MH  - Gene Knockout Techniques
MH  - Immunoglobulin E/blood/immunology
MH  - Langerhans Cells/*immunology/metabolism
MH  - Lectins, C-Type/metabolism
MH  - Mannose-Binding Lectins/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Ovalbumin/administration & dosage/immunology
MH  - Receptors, Aryl Hydrocarbon/genetics/*metabolism
MH  - T-Lymphocytes, Regulatory/*immunology/metabolism
MH  - Th2 Cells/*immunology/metabolism
PMC - PMC7293700
OTO - NOTNLM
OT  - Langerhans cells
OT  - Th2
OT  - Tr1
OT  - aryl hydrocarbon receptor
OT  - epicutaneous protein sensitization
COIS- The authors declare no competing interest.
EDAT- 2020/05/29 06:00
MHDA- 2020/08/22 06:00
PMCR- 2020/11/27
CRDT- 2020/05/29 06:00
PHST- 2020/05/29 06:00 [pubmed]
PHST- 2020/08/22 06:00 [medline]
PHST- 2020/05/29 06:00 [entrez]
PHST- 2020/11/27 00:00 [pmc-release]
AID - 1917479117 [pii]
AID - 201917479 [pii]
AID - 10.1073/pnas.1917479117 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2020 Jun 9;117(23):12980-12990. doi: 
      10.1073/pnas.1917479117. Epub 2020 May 27.