Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma

Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocu...

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Published in:Nature communications Vol. 9; no. 1; pp. 3209 - 13
Main Authors: Chen, Huihui, Cho, Kin-Sang, Vu, T. H. Khanh, Shen, Ching-Hung, Kaur, Mandeep, Chen, Guochun, Mathew, Rose, McHam, M. Lisa, Fazelat, Ahad, Lashkari, Kameran, Au, Ngan Pan Bennett, Tse, Joyce Ka Yu, Li, Yingqian, Yu, Honghua, Yang, Lanbo, Stein-Streilein, Joan, Ma, Chi Him Eddie, Woolf, Clifford J., Whary, Mark T., Jager, Martine J., Fox, James G., Chen, Jianzhu, Chen, Dong F.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 10.08.2018
Nature Publishing Group
Nature Portfolio
Subjects:
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Animals
Antigens
Axons - pathology
Blindness
Degeneration
Female
Germ-Free Life
Glaucoma
Glaucoma - complications
Glaucoma - immunology
Glaucoma - pathology
Glaucoma - physiopathology
Heat shock proteins
Heat-Shock Proteins - metabolism
Humanities and Social Sciences
Humans
Infiltration
Intraocular Pressure
Lymphocytes
Lymphocytes B
Lymphocytes T
Male
Mice
Mice, Inbred C57BL
Microbiota
Microflora
multidisciplinary
Nerve Degeneration - complications
Nerve Degeneration - immunology
Nerve Degeneration - pathology
Nerve Degeneration - physiopathology
Neurodegeneration
Retina
Retinal Ganglion Cells - pathology
Science
Science (multidisciplinary)
T cell receptors
T-Lymphocytes - immunology
Target recognition
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ganglion cell degeneration that persists after IOP returns to a normal level. Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma patients. Furthermore, retina-infiltrating T cells cross-react with human and bacterial HSPs; mice raised in the absence of commensal microflora do not develop glaucomatous T-cell responses or the associated neurodegeneration. These results provide compelling evidence that glaucomatous neurodegeneration is mediated in part by T cells that are pre-sensitized by exposure to commensal microflora. Glaucoma is a neurodegenerative disease of which the etiology is still unclear. Here the authors show that elevation of intraocular pressure induces T cell infiltration in the eyes. Furthermore, they show that T cell cross-reactivity between endogenous and commensal antigens contributes to disease onset in mice.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-05681-9