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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Vydané v:	Nature communications Ročník 9; číslo 1; s. 3209 - 13
Hlavní autori:	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.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 10.08.2018 Nature Publishing Group Nature Portfolio
Predmet:	13/21 13/31 13/51 14/19 14/28 14/63 38/88 631/250/1619/554 631/250/347 631/250/371 631/378/2613/1786 64/110 82/29 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
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-018-05681-9