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Langerhans cells prevent subbasal nerve damage and upregulate neurotrophic factors in dry eye disease

 Eun Young Choi  ;  Hyun Goo Kang  ;  Chul Hee Lee  ;  Areum Yeo  ;  Hye Mi Noh  ;  Nayeong Gu  ;  Myoung Joon Kim  ;  Jong Suk Song  ;  Hyeon Chang Kim  ;  Hyung Keun Lee 
 PLOS ONE, Vol.12(4) : e0176153, 2017 
Journal Title
Issue Date
Adult ; Aged ; Animals ; Antigens, Surface/genetics ; Antigens, Surface/metabolism ; Case-Control Studies ; Cell Count ; Cross-Sectional Studies ; Cytokines/metabolism ; Disease Models, Animal ; Dry Eye Syndromes/metabolism* ; Dry Eye Syndromes/pathology ; Female ; Humans ; Inflammation/metabolism ; Inflammation/pathology ; Langerhans Cells/metabolism* ; Lectins, C-Type/genetics ; Lectins, C-Type/metabolism ; Male ; Mannose-Binding Lectins/genetics ; Mannose-Binding Lectins/metabolism ; Mice ; Microscopy, Confocal ; Middle Aged ; Nerve Growth Factors/metabolism* ; Up-Regulation ; Young Adult
The functional role of Langerhans cells (LCs) in ocular surface inflammation and nerve damage in dry eye (DE) disease has yet to be determined. This study was performed to investigate this relationship through both clinical study on DE patients and in vivo mouse models with induced DE disease. In a cross-sectional case-control study (54 eyes of DE patients; 34 eyes of control patients), average cell density, area, and process length of LCs were measured using confocal microscopy. Data were analyzed to determine whether changes in LCs are correlated with subbasal nerve plexus (SNP) parameters (nerve density, beading, and tortuosity). In DE patients, SNP density marginally decreased and nerve beading and tortuosity were significantly increased compared to the control group. The total number of LCs significantly increased in DE patients, and some LCs with elongated processes were found to be attached to nerve fibers. Interestingly, nerve loss and deformation were correlated with inactivation of LCs. In an in vivo experiment to elucidate the role of LCs in ocular surface inflammation and corneal nerve loss, we used a genetically modified mouse model (CD207-DTR) that reduced the population of CD207 (Langerin) expressing cells by injection of diphtheria toxin. In CD207-depleted mice with DE disease (CD207-dDTR+DE), corneal nerves in the central region were significantly decreased, an effect that was not observed in wild-type (WT)+DE mice. In CD207-dDTR+DE mice, infiltration of CD4+, CD19+, CD45+, and CD11b+ cells into the ocular surface was increased, as confirmed by flow cytometry. Increased IL-17 and IFN-γ mRNA levels, and decreased expression of neurotrophic factors and neurotransmitters, were also found in the CD207-dDTR+DE mice. These data support a functional role for LCs in negatively regulating ocular surface inflammation and exhibiting a neuroprotective function in DE disease.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine (예방의학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hyun Goo(강현구) ORCID logo https://orcid.org/0000-0001-8359-9618
Kim, Hyeon Chang(김현창) ORCID logo https://orcid.org/0000-0001-7867-1240
Lee, Chul Hee(이철희)
Lee, Hyung Keun(이형근) ORCID logo https://orcid.org/0000-0002-1123-2136
Choi, Eun Young(최은영) ORCID logo https://orcid.org/0000-0002-1668-6452
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