Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma
| Autor: | Clifford J. Woolf, Kin-Sang Cho, Chi Him Eddie Ma, Jianzhu Chen, James G. Fox, Martine J. Jager, Guochun Chen, Dong Feng Chen, Ching-Hung Shen, Ngan Pan Bennett Au, M. Lisa McHam, Kameran Lashkari, Mark T. Whary, Joan Stein-Streilein, Honghua Yu, Ahad Fazelat, Yingqian Li, T. H. Khanh Vu, Huihui Chen, Mandeep Kaur, Joyce Ka Yu Tse, Lanbo Yang, Rose Mathew |
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| Přispěvatelé: | 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, Shen, Chase, Kaur, Mandeep, Whary, Mark T, Fox, James G |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Retinal Ganglion Cells Adoptive cell transfer genetic structures T cell T-Lymphocytes Science General Physics and Astronomy General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Antigen Heat shock protein medicine Animals Germ-Free Life Humans lcsh:Science Heat-Shock Proteins Intraocular Pressure Retina Multidisciplinary business.industry Microbiota Neurodegeneration Glaucoma General Chemistry medicine.disease Axons eye diseases 3. Good health Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Neuroimmunology Retinal ganglion cell Immunology Nerve Degeneration 030221 ophthalmology & optometry lcsh:Q Female sense organs business |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) Nature Nature Communications, 9 Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. National Institutes of Health (U.S.) (Grant EY025913) National Institutes of Health (U.S.) (Grant EY027067) National Institutes of Health (U.S.) (Grant EY025259) National Institutes of Health (U.S.) (Grant NS038253) National Institutes of Health (U.S.) (Grant AI69208) |
| Databáze: | OpenAIRE |
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