Parabiosis reveals the correlation between the recruitment of circulating antigen presenting cells to the retina and the induction of spontaneous autoimmune uveoretinitis.

Autor: McPherson SW; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 2001 6th Street SE, Lions Research Building, Room 482A, Minneapolis, MN, 55455, USA. mcphe003@umn.edu., Heuss ND; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 2001 6th Street SE, Lions Research Building, Room 482A, Minneapolis, MN, 55455, USA., Abedin M; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 2001 6th Street SE, Lions Research Building, Room 482A, Minneapolis, MN, 55455, USA., Roehrich H; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 2001 6th Street SE, Lions Research Building, Room 482A, Minneapolis, MN, 55455, USA., Pierson MJ; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 2001 6th Street SE, Lions Research Building, Room 482A, Minneapolis, MN, 55455, USA., Gregerson DS; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 2001 6th Street SE, Lions Research Building, Room 482A, Minneapolis, MN, 55455, USA.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2022 Dec 09; Vol. 19 (1), pp. 295. Date of Electronic Publication: 2022 Dec 09.
DOI: 10.1186/s12974-022-02660-2
Abstrakt: Background: Characterizing immune cells and conditions that govern their recruitment and function in autoimmune diseases of the nervous system or in neurodegenerative processes is an area of active investigation. We sought to analyze the origin of antigen presenting cells associated with the induction of retinal autoimmunity using a system that relies on spontaneous autoimmunity, thus avoiding uncertainties associated with immunization with adjuvants at remotes sites or adoptive transfer of in vitro activated T cells.
Methods: R161H mice (B10.RIII background), which spontaneously and rapidly develop severe spontaneous autoimmune uveoretinitis (SAU), were crossed to CD11c DTR/GFP mice (B6/J) allowing us to track the recruitment to and/or expansion within the retina of activated, antigen presenting cells (GFP hi cells) in R161H +/-  × CD11c DTR/GFP F 1 mice relative to the course of SAU. Parabiosis between R161H +/-  × CD11c DTR/GFP F 1 mice and B10.RIII × B6/J F 1 (wild-type recipient) mice was done to explore the origin and phenotype of antigen presenting cells crucial for the induction of autoimmunity. Analysis was done by retinal imaging, flow cytometry, and histology.
Results: Onset of SAU in R161H +/-  × CD11c DTR/GFP F 1 mice was delayed relative to B10.RIII-R161H +/- mice revealing a disease prophase prior to frank autoimmunity that was characterized by expansion of GFP hi cells within the retina prior to any clinical or histological evidence of autoimmunity. Parabiosis between mice carrying the R161H and CD11c DTR/GFP transgenes and transgene negative recipients showed that recruitment of circulating GFP hi cells into retinas was highly correlative with the occurrence of SAU.
Conclusions: Our results here contrast with our previous findings showing that retinal antigen presenting cells expanding in response to either sterile mechanical injury or neurodegeneration were derived from myeloid cells within the retina or optic nerve, thus highlighting a unique facet of retinal autoimmunity.
(© 2022. The Author(s).)
Databáze: MEDLINE
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