Background MDSCs (characterized in mice as CD11b+Gr1+ and in humans as CD14-HLA-DRlowCD15+CD33+) represent a phenotypically heterogeneous population of myeloid precursors of macrophages, dendritic cells and granulocytes. In EAE we have previously shown that immunization in the presence of Complete Freund’s Adjuvant (CFA) leads to expansion of MDSCs with a potent regulatory role in suppressing T-cell responses. Moreover, in patients with multiple sclerosis (MS) disease activity correlates with expansion of these cells and remission1.
Objectives To examine whether defective MDSCs may facilitate aberrant immune responses in murine and human systemic lupus erythematosus (SLE).
Methods We used the lupus prone (NZB x NZW) F1 female mice [3 months old, pre-SLE (n=6) and 6-8 months old, SLE mice (n=6)]. C57BL/6 (B6) female mice [3 mo (n=2) or 6 mo (n=6)] were used as controls. B6 mice immunized with myelin peptide (MOG) in CFA (Experimental Autoimmune Encephalomyelitis) were used as a disease control (n=3). To phenotype MDSCs in F1 under different immune context we injected F1 mice (n=3, 2 mo) with CFA. Cells were isolated from the bone marrow and spleen of the indicated groups and were stained with fluorescent-conjugated antibodies for the aforementioned markers and for 7AAD. Analysis was performed in humans as well, using samples from SLE patients (n=29) and healthy controls (n=26). Phenotyping and enumeration of cell populations were performed by flow cytometry.
Results Analysis of spleen as well as bone marrow of diseased (6-8 mo) and healthy (3 mo) F1 lupus-prone mice revealed no significant differences in the frequency of MDSCs. However, immunization of pre-diseased F1 mice with CFA resulted in significant expansion of MDSCs; the effect was comparable to the one observed in MOG/CFA-injected B6 mice, suggesting that the MDSC compartment does not respond in lupus inflammatory milieu. Furthermore, in human SLE, we observed no significant difference between active (median 6330±4097, N=13) and inactive patients (4835±2909, N=16), corroborating the murine data for a defective expansion of these cells in this disease.
Conclusions Together these data indicate an impaired MDSC expansion in the lupus, which may contribute to the aberrant immune responses in this disease. Ongoing experiments explore whether this is also associated with a defective function of MDSCs and the mechanisms involved.
Ioannou M, T Alissafi, I Lazaridis, G Derao, J Matsoukas, A Gravanis, V Mastorodemos, A Plaitakis, A Sharpe, D Boumpas, P Verginis. 2012. Crucial role of granulocytic myeloid-derived suppressor cells in the regulation of central nervous system autoimmune disease. J Immunol 188(3):1136-46.
Disclosure of Interest None Declared
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