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

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Abstract

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 CD11cDTR/GFP mice (B6/J) allowing us to track the recruitment to and/or expansion within the retina of activated, antigen presenting cells (GFPhi cells) in R161H+/− × CD11cDTR/GFP F1 mice relative to the course of SAU. Parabiosis between R161H+/− × CD11cDTR/GFP F1 mice and B10.RIII × B6/J F1 (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+/− × CD11cDTR/GFP F1 mice was delayed relative to B10.RIII-R161H+/− mice revealing a disease prophase prior to frank autoimmunity that was characterized by expansion of GFPhi cells within the retina prior to any clinical or histological evidence of autoimmunity. Parabiosis between mice carrying the R161H and CD11cDTR/GFP transgenes and transgene negative recipients showed that recruitment of circulating GFPhi 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.

Original languageEnglish (US)
Article number295
JournalJournal of Neuroinflammation
Volume19
Issue number1
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
This work was supported by the US National Institutes of Health (RO1-EY025209 and RO1-EY021003 to DSG, RO1-EY033328 to SWM, and P30-EY011374 to the University of Minnesota), The Wallin Neuroscience Discovery Fund, Research to Prevent Blindness, Inc., and the Minnesota Lions Clubs.

Publisher Copyright:
© 2022, The Author(s).

Keywords

  • Antigen presenting cells
  • Autoimmunity
  • Microglia
  • Origin
  • Parabiosis
  • Retina

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