Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma
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s41467-018-05681-9.pdf
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Author(s)
Chen, Huihui
Cho, Kin-Sang
Vu, T. H. Khanh
Chen, Guochun
Mathew, Rose
McHam, M. Lisa
Fazelat, Ahad
Lashkari, Kameran
AU, Ngan Pan Bennett
TSE, Joyce Ka Yu
Date Issued
August 2018
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Chen, Huihui et al. “Commensal Microflora-Induced T Cell Responses Mediate Progressive Neurodegeneration in Glaucoma.” Nature Communications 9, 1 (August 2018): 3209 © 2018 The Author(s)
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Division of Comparative Medicine
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/s41467-018-05681-9
