Immune Tolerance to HSP60 Attenuates Neurodegeneration in Glaucoma

Our previous study suggests that CD4+ T cells primed by bacterial heat shock proteins (HSP) mediate an autoimmune mechanism contributing to the pathogenesis of glaucoma. The present study showed that the activity of CD4+ T cells from the peripheral blood mononuclear cells (PBMC) of POAG patients was significantly higher than control subjects as revealed by single-cell RNA sequencing. The notion of antigenic mimicry between gut bacteria and mouse HSPs expressed in the eye causes glaucomatous degeneration remains unclear. Here, we report that the induction of immune tolerance by nasal administration of bacterial HSP60 protein led to an increase in regulatory T (Tr1) cells and suppression of HSP-specific Th1 cell frequencies in glaucoma mice. leading to protections against retinal ganglion cell loss and preservation of spatial vision in glaucoma mice. Moreover, this neuroprotective effect on retinal ganglion cells in HSP-immune-tolerant mice was compromised by IL-10 deficiency. Our data suggests that induction of immune tolerance to HSP60 presents a potential therapeutic strategy protecting against retinal degeneration and vision loss in glaucoma by partial restoration of T cell-mediated immune balance. Detailed information: https://github.com/mcrewcow/PBMC_Glaucoma_human CellXGene web-browser: https://cellxgene.cziscience.com/collections/de2cde16-c8d3-4a6d-80be-1be9e879aaca Overall design: Compare the gene expression of PBMC collected from 3 control subjects and 5 patients with primary open angle glaucoma.