000196750 001__ 196750
000196750 005__ 20190316235841.0
000196750 0247_ $$2doi$$a10.1172/Jci71488
000196750 022__ $$a0021-9738
000196750 02470 $$2ISI$$a000329333500044
000196750 037__ $$aARTICLE
000196750 245__ $$aLRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis
000196750 269__ $$a2014
000196750 260__ $$bAmerican Society for Clinical Investigation$$c2014$$aAnn Arbor
000196750 300__ $$a13
000196750 336__ $$aJournal Articles
000196750 520__ $$aCorneal 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 corned 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 corned-tissue transparency and cell fate during repair, and identify LRIG1 as a key regulator of tissue homeostasis.
000196750 700__ $$uKyoto Prefectural Univ Med, Grad Sch Med, Dept Ophthalmol, Kyoto 6020841, Japan$$aNakamura, Takahiro
000196750 700__ $$0240648$$g149977$$uEcole Polytech Fed Lausanne, Sch Life Sci, Lab Stem Cell Dynam, Lausanne, Switzerland$$aHamuro, Junji
000196750 700__ $$uKochi Univ, Kochi Med Sch, Dept Dermatol, Nankoku, Kochi, Japan$$aTakaishi, Mikiro
000196750 700__ $$uOsaka Univ, World Premier Int Res Ctr, Ctr Initiat Immunol Frontier Res Ctr, Lab Cellular Dynam, Osaka, Japan$$aSimmons, Szandor
000196750 700__ $$uKyoto Prefectural Univ Med, Grad Sch Med, Dept Ophthalmol, Kyoto 6020841, Japan$$aMaruyama, Kazuichi
000196750 700__ $$0245747$$g170947$$uEcole Polytech Fed Lausanne, Sch Life Sci, Lab Stem Cell Dynam, Lausanne, Switzerland$$aZaffalon, Andrea
000196750 700__ $$uUniv Lancaster, Sch Hlth & Med, Lancaster, England$$aBentley, Adam J.
000196750 700__ $$uKyoto Prefectural Univ Med, Grad Sch Med, Dept Ophthalmol, Kyoto 6020841, Japan$$aKawasaki, Satoshi
000196750 700__ $$uKyoto Prefectural Univ Med, Grad Sch Med, Dept Ophthalmol, Kyoto 6020841, Japan$$aNagata-Takaoka, Maho
000196750 700__ $$uUniv Lancaster, Sch Hlth & Med, Lancaster, England$$aFullwood, Nigel J.
000196750 700__ $$aItami, Satoshi
000196750 700__ $$uKochi Univ, Kochi Med Sch, Dept Dermatol, Nankoku, Kochi, Japan$$aSano, Shigetoshi
000196750 700__ $$uOsaka Univ, World Premier Int Res Ctr, Ctr Initiat Immunol Frontier Res Ctr, Lab Cellular Dynam, Osaka, Japan$$aIshii, Masaru
000196750 700__ $$g149977$$uEcole Polytech Fed Lausanne, Sch Life Sci, Lab Stem Cell Dynam, Lausanne, Switzerland$$aBarrandon, Yann$$0240648
000196750 700__ $$aKinoshita, Shigeru$$uKyoto Prefectural Univ Med, Grad Sch Med, Dept Ophthalmol, Kyoto 6020841, Japan
000196750 773__ $$j124$$tJournal Of Clinical Investigation$$k1$$q385-397
000196750 8564_ $$uhttps://infoscience.epfl.ch/record/196750/files/JCI71488.pdf$$zPublisher's version$$s8786818$$yPublisher's version
000196750 909C0 $$xU10462$$0252337$$pLDCS
000196750 909CO $$ooai:infoscience.tind.io:196750$$qGLOBAL_SET$$pSV$$particle
000196750 917Z8 $$x149977
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000196750 937__ $$aEPFL-ARTICLE-196750
000196750 973__ $$rREVIEWED$$sPUBLISHED$$aOTHER
000196750 980__ $$aARTICLE