FoxP3 expression by retinal pigment epithelial cells: transcription factor with potential relevance for the pathology of age-related macular degeneration

• DOI: 10.1186/s12974-022-02620-w
• Publication Date: 2022-10-22T13:05:13Z
• Authors: Ahmad Samir Alfaar; Lucas Stürzbecher; Maria Diedrichs-M...; Marion Lam; Christophe Roubeix; Julia Ritter; Kathrin Schumann; Balasubramaniam A...; Inga-Marie Pompös; Bärbel Rohrer; Florian Sennlaub; Nadine Reichhart; Gerhild Wildner; Olaf Strauß
• Keywords: Degeneration (medical)

Abstract Background Forkhead-Box-Protein P3 (FoxP3) is a transcription factor and marker of regulatory T cells, converting naive cells into Tregs that can downregulate the effector function other cells. We previously detected expression FoxP3 in retinal pigment epithelial (RPE) forming outer blood–retina barrier immune privileged eye. Methods investigated expression, subcellular localization, phosphorylation RPE vivo vitro after treatment with various stressors including age, laser burn, autoimmune inflammation, exposure to cigarette smoke, addition IL-1β mechanical cell monolayer destruction. Eye tissue from humans, mouse models degeneration rats, ARPE-19, human line for experiments, underwent immunohistochemical, immunofluorescence staining, PCR or immunoblot analysis determine intracellular localization FoxP3. Cytokine stressed cultured was by multiplex bead analysis. Depletion gene performed CRISPR/Cas9 editing. Results displayed increased nuclear FoxP3-expression increases age long-term mice burn injury. The ARPE-19 constitutively expressed under non-confluent culture conditions, representing phenotype chronic stress. Confluently grown cytosolic translocated nucleus imitate activated macrophages destruction monolayer. Moreover, depletion FoxP3, but not control gene, editing decreased stress resistance Conclusion Our data suggest upregulated cellular might be important function.