Autoimmune neurologic diseases

Oral

Regulation of Myeloid Cells Function by Nanoparticles

Thursday, June 15
5:45 PM - 7:00 PM

Antigen-presenting cells (APCs) makeup a significant proportion of the cells found within lesions of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). These APCs have the ability to capture myelin debris and to promote either an inflammatory response or a tolerogenic response from the effector lymphocytes. In MS patients and EAE animals, APCs induce an inflammatory response.


Recently, the Miller laboratory showed that intravenous (i.v.) injection of myelin antigen-coupled nanoparticles (Ag-NPs) made from the copolymers of lactic and glycolic acid (PLG) could prevent the onset of EAE and, more importantly, attenuate active disease. Our goal was to understand by which mechanism these NPs modulate the immune response and induce T cell tolerance.


We found that all CD11b+ myeloid cells are taken up NPs, as early as 30 minutes after i.v. injection, with mDCs and inflammatory monocytes being the most efficient cells. Interestingly, microglia are unable to engulf NPs in vitro. Moreover, immunofluorescence analysis shows that NPs accumulated at 3h in the spleen, but were largely undetectable 24h post-injection. After ingestion of NPs, myeloid cells decrease their expression level of costimulatory molecules CD80, CD86 and CD40, as well as the cytokines IL-12, IL-23 and TNF. In addition, CD4+ T cells co-cultured in presence of APCs, which have uptaken NPs, produce reduced levels of IL-17 and GM-CSF, and exhibit increased expression of TGF-beta, CTLA-4 and PD-1.


Collectively our data demonstrate that NPs are captured by APCs, which subsequently change their phenotype and function to an immune regulatory profile.

Igal Ifergan

Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University

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    Dan Xu

    Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University

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      Stephen D. Miller

      Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University

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