P006. Regulation of inflammatory bowel diseases by myeloid-derived suppressor cells
E. Kontaki1, M. Ioannou1, T. Alissafi1, L. Boon2, D. Boumpas1, K. Papadakis1, P. Verginis1
1University of Crete Medical School, Greece; 2Biokeros, Utrecht, Netherlands
Background: Restoration of immune homeostasis and self-tolerance represent the ultimate goal of autoimmune diseases. Although a variety of therapeutic targets are employed, a large number of patients with autoimmune syndromes fail to either respond to current therapy or to achieve long-lasting remission after its cessation. Myeloid-derived suppressor cells (MDSCs) encompass a newly described population of cells that potently suppress immune responses; however their role in autoimmune inflammatory diseases is poorly understood.
Methods: Using flow cytometry, we assessed the presence of human MDSCs, denoted as CD14-HLA-DR-/lowCD15+CD33+cells, in peripheral blood from patients with active Crohn's disease (CD) and ulcerative colitis. Further, we monitored the expansion of CD11b+Gr1+ MDSCs in peripheral lymphoid compartments of mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Following, we evaluated the disease progress after in vivo depletion of MDSCs, by using anti-Gr1 mAb (RB68C5).
Results: We observed that CD15+CD33+ MDSCs are significantly enriched in the periphery of subjects with active CD compared to healthy controls (4.336±0.8747 vs 14.34±2.462, ***p < 0.0001). In addition, Gr1+CD11bhi MDSCs are largely accumulated in the spleen of mice with experimental colitis, during the effector phase of the disease, while they contracted upon disease resolution (5.328±0.7109 vs 1.170±0.2740, **p < 0.0055). Importantly, anti-Gr1 mAb mediated depletion of MDSCs aggravated the colitic phenotype. These findings suggest that MDSCs might play an important role in the regulation of TNBS-induced colitis.
Conclusions: Our data demonstrate a significant enrichment of MDSCs in the periphery of CD patients, as well as the peripheral lymphoid compartments of colitic mice. Since MDSCs are bone marrow (BM) resident cells, ongoing work would address the potential role of BM-derived MDSCs in inhibiting established disease and elucidate the mechanisms used by MDSCs for the suppression of inflammatory bowel diseases.