Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid.

Autor:	Lehmann GL; Department of Ophthalmology, Margaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY.; Regeneron Pharmaceuticals, Inc., Tarrytown, NY., Hanke-Gogokhia C; Department of Ophthalmology, Margaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY., Hu Y; Caryl and Israel Englander Institute for Precision Medicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY., Bareja R; Caryl and Israel Englander Institute for Precision Medicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY., Salfati Z; Department of Ophthalmology, Margaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY., Ginsberg M; Angiocrine Bioscience, Inc., San Diego, CA., Nolan DJ; Angiocrine Bioscience, Inc., San Diego, CA., Mendez-Huergo SP; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina., Dalotto-Moreno T; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina., Wojcinski A; Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY., Ochoa F; Regeneron Pharmaceuticals, Inc., Tarrytown, NY., Zeng S; The University of Iowa Institute for Vision Research and Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, IA., Cerliani JP; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina., Panagis L; Regeneron Pharmaceuticals, Inc., Tarrytown, NY., Zager PJ; Department of Ophthalmology, Margaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY., Mullins RF; The University of Iowa Institute for Vision Research and Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, IA., Ogura S; Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD., Lutty GA; Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD., Bang J; Department of Dermatology, Weill Cornell Medicine and New York-Presbyterian Hospital, New York, NY., Zippin JH; Department of Dermatology, Weill Cornell Medicine and New York-Presbyterian Hospital, New York, NY., Romano C; Regeneron Pharmaceuticals, Inc., Tarrytown, NY., Rabinovich GA; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina., Elemento O; Caryl and Israel Englander Institute for Precision Medicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY., Joyner AL; Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY., Rafii S; Ansary Stem Cell Institute, Department of Medicine, Division of Regenerative Medicine, Weill Cornell Medicine, New York, NY., Rodriguez-Boulan E; Department of Ophthalmology, Margaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY., Benedicto I; Department of Ophthalmology, Margaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY.; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2020 Jun 01; Vol. 217 (6).
DOI:	10.1084/jem.20190730
Abstrakt:	The activity and survival of retinal photoreceptors depend on support functions performed by the retinal pigment epithelium (RPE) and on oxygen and nutrients delivered by blood vessels in the underlying choroid. By combining single-cell and bulk RNA sequencing, we categorized mouse RPE/choroid cell types and characterized the tissue-specific transcriptomic features of choroidal endothelial cells. We found that choroidal endothelium adjacent to the RPE expresses high levels of Indian Hedgehog and identified its downstream target as stromal GLI1+ mesenchymal stem cell-like cells. In vivo genetic impairment of Hedgehog signaling induced significant loss of choroidal mast cells, as well as an altered inflammatory response and exacerbated visual function defects after retinal damage. Our studies reveal the cellular and molecular landscape of adult RPE/choroid and uncover a Hedgehog-regulated choroidal immunomodulatory signaling circuit. These results open new avenues for the study and treatment of retinal vascular diseases and choroid-related inflammatory blinding disorders. Competing Interests: Disclosures: Dr. Nolan reported personal fees from Angiocrine Bioscience during the conduct of the study; in addition, Dr. Nolan had a patent number 9,944,897 issued "Angiocrine Bioscience." Dr. Panagis reported personal fees from Regeneron outside the submitted work. Dr. Zippin reported grants from Pfizer and personal fees from Hoth outside the submitted work. Dr. Romano reported, "I am an employee of Regeneron Pharmaceuticals, however there are no products or services of this company related to the work presented in this manuscript." Dr. Elemento reported "other" from Volastra Therapeutics, "other" from One Three Biotech, "other" from Freenome, and "other" from Owkin outside the submitted work. Dr. Rafii reported non-financial support from Angiocrine BioScience during the conduct of the study. No other disclosures were reported. (© 2020 Lehmann et al.)
Databáze:	MEDLINE
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