CSF1R blockade improves clinical parameters in prediabetic rhesus macaques

• Published in: The Journal of immunology (1950) Vol. 210; no. 1_Supplement; pp. 155 - 155.09
• Main Authors: Stahr, Natalie Ann, Phou, Amy, Hattler, Julian, McGuire, David, Kim, Woong-Ki
• Format: Journal Article
• Language: English
• Published: 01-05-2023
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.210.Supp.155.09

It is unknown whether dysregulated CSF1R himonocytes/macrophages drive the progression to diabetes and if their removal and endogenous replacement with fresh macrophages resolves disease. Therefore, we hypothesize that depletion of activated CSF1R+ tissue macrophages using a monoclonal antibody against CSF1R and replacement with freshly differentiated macrophages will alleviate inflammation in tissues and ameliorate diabetes-associated disease in prediabetic rhesus macaques.
We identified 6 aged Indian rhesus macaques with heightened fasting blood glucose as well as higher area-under-the-curve in an intravenous glucose tolerance test (IVGTT), indicating prediabetes. Three animals were treated with a rhesus IgG1 recombinantanti-CSF1R antibody administered i.v. (15 mg/kg) once every two weeks for 6 weeks. An IgG1 control was administered to the remaining 3 animals. Clinical parameters such as blood pressure, plasma levels of total cholesterol, glucose, insulin, adiponectin, colony stimulating factor 1 (CSF1), IL1β, monocyte chemoattractant protein 1 (MCP-1) were monitored throughout treatment and up to 8 weeks after the 3 rdinjection. A 27-color flow cytometry panel were used to monitor changes in immune cell populations throughout the study.
Treatment with anti-CSF1R resulted in decreased total cholesterol, increased adiponectin, increased CSF1, and increased IL1β levels in the blood throughout the study. Flow cytometry experiments confirmed the depletion of CD16+ monocytes (known to be CSF1R +) in treated animals.
Treatment with anti-CSF1R resulted in improvement in multiple clinical parameters associated with the progression to type-2 diabetes mellitus.