CD47 Deficiency Ameliorates Ocular Autoimmune Inflammation.

Yoko Okunuki,Steven J Tabor,May Y Lee,Kip M Connor

doi:10.3389/fimmu.2021.680568

Yoko Okunuki, Steven J Tabor + Show 2 more

Open Access

https://doi.org/10.3389/fimmu.2021.680568

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Abstract

Autoimmune uveitis is a sight-threatening ocular inflammatory condition in which the retina and uveal tissues become a target of autoreactive immune cells. The CD47 is a ubiquitously expressed transmembrane protein which plays multiple roles in fundamental cellular functions including phagocytosis, proliferation, and adhesion. Signal regulatory protein alpha (SIRPα), one of the CD47 ligands, is predominantly expressed in myeloid lineage cells such as dendritic cells (DCs) or macrophages, and CD47-SIRPα signaling pathway is implicated in the development of autoimmune diseases. Our current study demonstrates how CD47 depletion is effective in the prevention of experimental autoimmune uveitis (EAU), an animal model of human autoimmune uveitis, in animals deficient of CD47 (CD47-/-). Systemic suppression of SIRPα+ DCs in animals deficient in CD47 resulted in the inability of autoreactive CD4+ T cells to develop, which is crucial to induction of EAU. Of interest, retinal microglia, the resident immune cell of the retina, express SIRPα, however these cells were not operative in EAU suppression in response to CD47 depletion. These results identify CD47 as a significant regulator in the development of SIRPα+ DCs that is vital to disease induction in EAU.

Highlights

Autoimmune uveitis, which occurs in a variety of diseases, including Bechet’s disease, sarcoidosis, and Vogt–Koyanagi–Harada disease, among many others, is a sight-threatening ocular inflammatory disease [1,2,3,4]
CD47 knockout (CD47-/-) mice were utilized and Experimental autoimmune uveitis (EAU) was induced by immunizing the animals with interphotoreceptor retinoid-binding protein (IRBP)-peptide 1–20 (IRBP-p) in both knockout animals and littermate wild type (WT) controls
IRBP-specific and non-specific in vitro lymphocyte proliferation using lymph node (LN) cells and spleen (SP) cells, isolated from mice with EAU at 14 days (Supplemental Figure S2) and 21 days (Figures 1F, G) post immunization was significantly reduced in CD47-/- mice

Summary

Introduction

Autoimmune uveitis, which occurs in a variety of diseases, including Bechet’s disease, sarcoidosis, and Vogt–Koyanagi–Harada disease, among many others, is a sight-threatening ocular inflammatory disease [1,2,3,4]. Autoimmune uveitis covers a range of different clinical entities, autoimmunity against the retina and the uveal tissues is thought to be fundamental to its pathogenesis [5]. EAU is induced by immunization against retinal antigens such as interphotoreceptor retinoid-binding protein (IRBP), which is a major component of photoreceptor outer segments. Uveitogenic antigen-specific CD4+ T-cells are crucial effector cells that drive inflammation and tissue damage after being activated by dendritic cells (DCs) [9].

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