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LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis

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LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis. / Nakamura, Takahiro; Hamuro, Junji; Takaishi, Mikiro; Simmons, Szandor; Maruyama, Kazuichi; Zaffalon, Andrea; Bentley, Adam J.; Kawasaki, Satoshi; Nagata-Takaoka, Maho; Fullwood, Nigel J.; Itami, Satoshi; Sano, Shigetoshi; Ishii, Masaru; Barrandon, Yann; Kinoshita, Shigeru.

In: Journal of Clinical Investigation, Vol. 124, No. 1, 02.01.2014, p. 385-397.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Nakamura, T, Hamuro, J, Takaishi, M, Simmons, S, Maruyama, K, Zaffalon, A, Bentley, AJ, Kawasaki, S, Nagata-Takaoka, M, Fullwood, NJ, Itami, S, Sano, S, Ishii, M, Barrandon, Y & Kinoshita, S 2014, 'LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis', Journal of Clinical Investigation, vol. 124, no. 1, pp. 385-397. https://doi.org/10.1172/JCI71488

APA

Nakamura, T., Hamuro, J., Takaishi, M., Simmons, S., Maruyama, K., Zaffalon, A., Bentley, A. J., Kawasaki, S., Nagata-Takaoka, M., Fullwood, N. J., Itami, S., Sano, S., Ishii, M., Barrandon, Y., & Kinoshita, S. (2014). LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis. Journal of Clinical Investigation, 124(1), 385-397. https://doi.org/10.1172/JCI71488

Vancouver

Nakamura T, Hamuro J, Takaishi M, Simmons S, Maruyama K, Zaffalon A et al. LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis. Journal of Clinical Investigation. 2014 Jan 2;124(1):385-397. https://doi.org/10.1172/JCI71488

Author

Nakamura, Takahiro ; Hamuro, Junji ; Takaishi, Mikiro ; Simmons, Szandor ; Maruyama, Kazuichi ; Zaffalon, Andrea ; Bentley, Adam J. ; Kawasaki, Satoshi ; Nagata-Takaoka, Maho ; Fullwood, Nigel J. ; Itami, Satoshi ; Sano, Shigetoshi ; Ishii, Masaru ; Barrandon, Yann ; Kinoshita, Shigeru. / LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis. In: Journal of Clinical Investigation. 2014 ; Vol. 124, No. 1. pp. 385-397.

Bibtex

@article{e54145d9b64a4f6fb5a23d060e0e00d3,
title = "LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis",
abstract = "Corneal integrity and transparency are indispensable for good vision. Cornea homeostasis is entirely dependent upon corneal stem cells, which are required for complex wound-healing processes that restore corneal integrity following epithelial damage. Here, we found that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is highly expressed in the human holoclone-type corneal epithelial stem cell population and sporadically expressed in the basal cells of ocular-surface epithelium. In murine models, LRIG1 regulated corneal epithelial cell fate during wound repair. Deletion of Lrig1 resulted in impaired stem cell recruitment following injury and promoted a cell-fate switch from transparent epithelium to keratinized skin-like epidermis, which led to corneal blindness. In addition, we determined that LRIG1 is a negative regulator of the STAT3-dependent inflammatory pathway. Inhibition of STAT3 in corneas of Lrig1-/- mice rescued pathological phenotypes and prevented corneal opacity. Additionally, transgenic mice that expressed a constitutively active form of STAT3 in the corneal epithelium had abnormal features, including corneal plaques and neovascularization similar to that found in Lrig1-/- mice. Bone marrow chimera experiments indicated that LRIG1 also coordinates the function of bone marrow-derived inflammatory cells. Together, our data indicate that LRIG1 orchestrates corneal-tissue transparency and cell fate during repair, and identify LRIG1 as a key regulator of tissue homeostasis.",
keywords = "Animals, Bone Marrow Transplantation, Cells, Cultured, Conjunctiva, Cornea, Epithelium, Corneal, Humans, Keratinocytes, Keratitis, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Nerve Tissue Proteins, STAT3 Transcription Factor, Stem Cells, Transcriptome, Wound Healing",
author = "Takahiro Nakamura and Junji Hamuro and Mikiro Takaishi and Szandor Simmons and Kazuichi Maruyama and Andrea Zaffalon and Bentley, {Adam J.} and Satoshi Kawasaki and Maho Nagata-Takaoka and Fullwood, {Nigel J.} and Satoshi Itami and Shigetoshi Sano and Masaru Ishii and Yann Barrandon and Shigeru Kinoshita",
year = "2014",
month = jan,
day = "2",
doi = "10.1172/JCI71488",
language = "English",
volume = "124",
pages = "385--397",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "1",

}

RIS

TY - JOUR

T1 - LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis

AU - Nakamura, Takahiro

AU - Hamuro, Junji

AU - Takaishi, Mikiro

AU - Simmons, Szandor

AU - Maruyama, Kazuichi

AU - Zaffalon, Andrea

AU - Bentley, Adam J.

AU - Kawasaki, Satoshi

AU - Nagata-Takaoka, Maho

AU - Fullwood, Nigel J.

AU - Itami, Satoshi

AU - Sano, Shigetoshi

AU - Ishii, Masaru

AU - Barrandon, Yann

AU - Kinoshita, Shigeru

PY - 2014/1/2

Y1 - 2014/1/2

N2 - Corneal integrity and transparency are indispensable for good vision. Cornea homeostasis is entirely dependent upon corneal stem cells, which are required for complex wound-healing processes that restore corneal integrity following epithelial damage. Here, we found that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is highly expressed in the human holoclone-type corneal epithelial stem cell population and sporadically expressed in the basal cells of ocular-surface epithelium. In murine models, LRIG1 regulated corneal epithelial cell fate during wound repair. Deletion of Lrig1 resulted in impaired stem cell recruitment following injury and promoted a cell-fate switch from transparent epithelium to keratinized skin-like epidermis, which led to corneal blindness. In addition, we determined that LRIG1 is a negative regulator of the STAT3-dependent inflammatory pathway. Inhibition of STAT3 in corneas of Lrig1-/- mice rescued pathological phenotypes and prevented corneal opacity. Additionally, transgenic mice that expressed a constitutively active form of STAT3 in the corneal epithelium had abnormal features, including corneal plaques and neovascularization similar to that found in Lrig1-/- mice. Bone marrow chimera experiments indicated that LRIG1 also coordinates the function of bone marrow-derived inflammatory cells. Together, our data indicate that LRIG1 orchestrates corneal-tissue transparency and cell fate during repair, and identify LRIG1 as a key regulator of tissue homeostasis.

AB - Corneal integrity and transparency are indispensable for good vision. Cornea homeostasis is entirely dependent upon corneal stem cells, which are required for complex wound-healing processes that restore corneal integrity following epithelial damage. Here, we found that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is highly expressed in the human holoclone-type corneal epithelial stem cell population and sporadically expressed in the basal cells of ocular-surface epithelium. In murine models, LRIG1 regulated corneal epithelial cell fate during wound repair. Deletion of Lrig1 resulted in impaired stem cell recruitment following injury and promoted a cell-fate switch from transparent epithelium to keratinized skin-like epidermis, which led to corneal blindness. In addition, we determined that LRIG1 is a negative regulator of the STAT3-dependent inflammatory pathway. Inhibition of STAT3 in corneas of Lrig1-/- mice rescued pathological phenotypes and prevented corneal opacity. Additionally, transgenic mice that expressed a constitutively active form of STAT3 in the corneal epithelium had abnormal features, including corneal plaques and neovascularization similar to that found in Lrig1-/- mice. Bone marrow chimera experiments indicated that LRIG1 also coordinates the function of bone marrow-derived inflammatory cells. Together, our data indicate that LRIG1 orchestrates corneal-tissue transparency and cell fate during repair, and identify LRIG1 as a key regulator of tissue homeostasis.

KW - Animals

KW - Bone Marrow Transplantation

KW - Cells, Cultured

KW - Conjunctiva

KW - Cornea

KW - Epithelium, Corneal

KW - Humans

KW - Keratinocytes

KW - Keratitis

KW - Membrane Glycoproteins

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Nerve Tissue Proteins

KW - STAT3 Transcription Factor

KW - Stem Cells

KW - Transcriptome

KW - Wound Healing

U2 - 10.1172/JCI71488

DO - 10.1172/JCI71488

M3 - Journal article

C2 - 24316976

VL - 124

SP - 385

EP - 397

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 1

ER -