Abstract Details

Title Monocyte Derived Myeloid Suppressor Cell Subsets in the Central Nervous System Infiltrating Cells are Distinct from these in Peripheral Blood of Mice with Experimental Autoimmune Encephalomyelitis

Topic Multiple Sclerosis

Presentation(s) MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 124

Objective

To characterize monocyte myeloid derived suppressor cells (M-MDSC) in central nervous system (CNS)’s immune compartment as compared with their circulating counterpart in the blood of mice with Experimental autoimmune encephalomyelitis (EAE).

Background EAE is a T cell-mediated autoimmune disease provoked by the peripheral innate immune system. Recently, controversial evidences for the role of M-MDSC in EAE were reported. Whether the circulating monocytes repertoire and particularly M-MDSC reflect the infiltrating counterparts in the CNS in terms of cytokine profile is undetermined.

Design/Methods EAE was induced by immunization of SJL/J mice with PLP135-151. Seven days after EAE onset, brain and spinal cord were isolated and after preparing single cell suspension, peripheral blood immune cells and CNS infiltrating immune cells were subjected for high-dimensional single-cell mass cytometry and compared with naïve mice. Data was analyzed by Cytobank software.

Results

Three populations of CD11b+CD45+ monocytes were identified. The naïve monocytes CD45+CD11+Ly6c-, pro-inflammatory CD45+CD11+Ly6c+, and M-MDSC; CD45+CD11+Ly6c++. The proportion of CD45+CD11+Ly6c- significantly increased in peripheral blood of mice displaying EAE by 66% (p<0.05), while in the CNS this population remained comparable. The pro-inflammatory population of CD45+CD11+Ly6c+ increased in blood by 83%, but decreased in the CNS by 34% (p<0.05). The less abundant CD45+CD11+Ly6c++ population also increased in blood by 87% (p<0.05), while in the CNS this population remained comparable. Interestingly, M-MDSC in the CNS show increased IL-10 (100%) and decreased TGFb (by 50%) while in blood this subset show significant increase in IL-17 (by 60%).

Conclusions

M-MDSC display opposing cytokine profile in the peripheral blood and the CNS, which may reflect their function in response to particular signals from the microenvironment.

Authors/Disclosures
Rina I. Falb, PhD (Medison Pharma) PRESENTER	Dr. Falb has nothing to disclose.
Michael Gurevich, MD (Sheba Medical Center)	Dr. Gurevich has nothing to disclose.
Anat Achiron, MD, PhD, FAAN (Sheba Medical Center, Tel-Hashomer)	Dr. Achiron has nothing to disclose.

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