Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma
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; Li, Yingqian; Yu, Honghua; Yang, Lanbo; Stein-Streilein, Joan; Ma, Chi Him Eddie; Woolf, Clifford J.; Jager, Martine J.; Chen, Jianzhu; Chen, Dong F.; Shen, Chase; Kaur, Mandeep; Whary, Mark T; Fox, James G; ... Show more Show less
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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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Division of Comparative Medicine
Nature Publishing Group
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)
Final published version