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, HyeonChang Kim, Hyung Keun Lee

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0176153
JournalPloS one
Volume12
Issue number4
DOIs
Publication statusPublished - 2017 Apr 1

Fingerprint

Langerhans cells
eye diseases
neurotrophins
Langerhans Cells
Eye Diseases
Nerve Growth Factors
nerve tissue
Up-Regulation
eyes
Diphtheria Toxin
Interleukin-17
Flow cytometry
Confocal microscopy
Infiltration
Neurotransmitter Agents
inflammation
plexus
mice
Messenger RNA
Inflammation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Choi, E. Y., Kang, H. G., Lee, C. H., Yeo, A., Noh, H. M., Gu, N., ... Lee, H. K. (2017). Langerhans cells prevent subbasal nerve damage and upregulate neurotrophic factors in dry eye disease. PloS one, 12(4), [e0176153]. https://doi.org/10.1371/journal.pone.0176153
Choi, Eun Young ; Kang, Hyun Goo ; Lee, Chul Hee ; Yeo, Areum ; Noh, Hye Mi ; Gu, Nayeong ; Kim, Myoung Joon ; Song, Jong Suk ; Kim, HyeonChang ; Lee, Hyung Keun. / Langerhans cells prevent subbasal nerve damage and upregulate neurotrophic factors in dry eye disease. In: PloS one. 2017 ; Vol. 12, No. 4.
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abstract = "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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Choi, EY, Kang, HG, Lee, CH, Yeo, A, Noh, HM, Gu, N, Kim, MJ, Song, JS, Kim, H & Lee, HK 2017, 'Langerhans cells prevent subbasal nerve damage and upregulate neurotrophic factors in dry eye disease', PloS one, vol. 12, no. 4, e0176153. https://doi.org/10.1371/journal.pone.0176153

Langerhans cells prevent subbasal nerve damage and upregulate neurotrophic factors in dry eye disease. / Choi, Eun Young; Kang, Hyun Goo; Lee, Chul Hee; Yeo, Areum; Noh, Hye Mi; Gu, Nayeong; Kim, Myoung Joon; Song, Jong Suk; Kim, HyeonChang; Lee, Hyung Keun.

In: PloS one, Vol. 12, No. 4, e0176153, 01.04.2017.

Research output: Contribution to journalArticle

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AU - Choi, Eun Young

AU - Kang, Hyun Goo

AU - Lee, Chul Hee

AU - Yeo, Areum

AU - Noh, Hye Mi

AU - Gu, Nayeong

AU - Kim, Myoung Joon

AU - Song, Jong Suk

AU - Kim, HyeonChang

AU - Lee, Hyung Keun

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AB - 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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