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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2022

Open Access 01-12-2022 | Research

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

Authors: Scott W. McPherson, Neal D. Heuss, Md. Abedin, Heidi Roehrich, Mark J. Pierson, Dale S. Gregerson

Published in: Journal of Neuroinflammation | Issue 1/2022

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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.
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Metadata
Title
Parabiosis reveals the correlation between the recruitment of circulating antigen presenting cells to the retina and the induction of spontaneous autoimmune uveoretinitis
Authors
Scott W. McPherson
Neal D. Heuss
Md. Abedin
Heidi Roehrich
Mark J. Pierson
Dale S. Gregerson
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2022
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-022-02660-2

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