Apolipoprotein A1 Modulates Teff/Treg Balance Through Scavenger Receptor Class B Type I-Dependent Mechanisms in Experimental Autoimmune Uveitis.

ABSTRACT:

Purpose

Experimental autoimmune uveitis (EAU) is a representative animal model of human uveitis. In this study, we investigated whether apolipoprotein A1 (APOA1) can alleviate EAU and explored its underlying mechanism.

Methods

Mice were immunized with interphotoreceptor retinoid-binding protein 1-20 and treated with APOA1 or vehicle. The retinas, draining lymph nodes (DLNs), and spleens were analyzed. Isolated T cells were used for proliferation, differentiation, and function assays in vitro. Selective inhibitors and pathway agonists were used to study signaling pathways. The effect of APOA1 on peripheral blood mononuclear cells (PBMCs) from uveitis patients was also examined.

Results

Administration of APOA1 ameliorated EAU. APOA1 suppressed pathogenic CD4+ T cell expansion in DLNs and spleen, and decreased the infiltration of effector T (Teff) cells into retina. APOA1 also inhibited T cell proliferation and T helper 1 cell differentiation in vitro and promoted regulatory T (Treg) cell differentiation. APOA1 restricted inflammatory cytokine production from lipopolysaccharide-stimulated PBMCs. Mechanistic studies revealed that the effect of APOA1 was mediated by scavenger receptor class B type I (SR-BI) and downstream signals including phosphatidylinositol 3-kinase/Protein kinase B (PKB, or Akt), p38 mitogen-activated protein kinase, and nuclear factor-κB.

Conclusions

APOA1 ameliorates EAU by regulating the Teff/Treg partially through SR-BI. Our results suggest that APOA1 can be a therapeutic alternative for autoimmune uveitis.

SUBMITTER: Huang H 

PROVIDER: S-EPMC9339694 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature