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

Scott W McPherson; Neal D Heuss; Md Abedin; Heidi Roehrich; Mark J Pierson; Dale S Gregerson

doi:10.1186/s12974-022-02660-2

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

J Neuroinflammation. 2022 Dec 9;19(1):295. doi: 10.1186/s12974-022-02660-2.

Authors

Scott W McPherson¹, Neal D Heuss², Md Abedin², Heidi Roehrich², Mark J Pierson², Dale S Gregerson²

Affiliations

¹ 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.
² Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 2001 6th Street SE, Lions Research Building, Room 482A, Minneapolis, MN, 55455, USA.

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 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 F₁ mice relative to the course of SAU. Parabiosis between R161H^+/- × CD11c^DTR/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^+/- × CD11c^DTR/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 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.

Keywords: Antigen presenting cells; Autoimmunity; Microglia; Origin; Parabiosis; Retina.

MeSH terms

Animals
Antigen-Presenting Cells
Autoimmune Diseases*
Disease Models, Animal
Mice
Mice, Inbred C57BL
Mice, Transgenic
Parabiosis
Retina* / pathology

Abstract

MeSH terms

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