Treating collagen induced arthritis CIA with immunoregulatory nanoparticles

DESCRIPTION provided by applicant The title of this project is andquot Treating Collagen induced Arthritis with Fc Receptor Activating Nanoparticlesandquot We and others have identified and characterized a population of macrophages with potent immunorergulatory activity The goal of the present proposal is to induce the production of regulatory macrophages R M in mice and determine whether their induction can decrease pathology associated with collagen induced arthritis CIA To induce R M mice will be injected with Fc Receptor Activating Nanoparticle Fc RANP We have established a collaborative arrangement in which LeukoSight will produce and purify proprietary polypeptides that bind to Fc receptors on macrophages In collaboration with Dr Christopher Jewell at the University of Maryland these polypeptides will be tethered to nanoparticles and tested for their ability to andquot reprogramandquot macrophages into R M Fc RANP with the highest reprogramming activity will then be tested in two models of CIA In the first model mice will be injected with Type II Collagen in CFA and then administered Fc RANP prior to the induction of disease A delay in the onset of disease or a decrease in severity will be measured over the next several weeks Aim In the second model clinically apparent CIA will be induced in mice by the injection of C II in CFA and then after the mice show symptoms of established disease they will be injected with Fc RANP Over the next two weeks the resolution of symptoms and a decrease in pathology will be examined and quantified Aim The decrease in pathology will be correlated with the appearance of R M in the joint synovium LeukoSight Inc has invested substantial time and effort into identifying recombinant polypeptides that bind avidly to macrophage Fc R and they have developed a reliable assay to measure regulatory macrophage andquot reprogrammingandquot The university research laboratories of Drs Mosser and Jewell have proficiency in a variety of autoimmune disease models including CIA The University has provided IACUC approval to perform these studies The goal of these studies is to demonstrate the feasibility of using nanoparticle based macrophage reprogramming as a therapeutic strategy to treat autoimmune diseases PUBLIC HEALTH RELEVANCE The title of this application is andquot Treating collagen induced arthritis CIA with immunoregulatory nanoparticlesandquot The goal of this application is to determine the feasibility of using nanoparticles to generate Regulatory macrophages to reverse autoimmune pathology in human rheumatoid arthritis using the collagen induced arthritis mouse model