LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis.

Details

Serval ID
serval:BIB_B22330EDB98A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis.
Journal
Journal of Clinical Investigation
Author(s)
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.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Publication state
Published
Issued date
2014
Volume
124
Number
1
Pages
385-397
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
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.
Pubmed
Web of science
Open Access
Yes
Create date
07/02/2014 18:35
Last modification date
20/08/2019 15:20
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