Journal of Clinical and Cellular Immunology
Open Access

Proinflammatory role of myeloid derived suppressor cells (MDSCs) in a glucose-6-phosphate isomerase (GPI)-induced T-cell and B-cell independent rheumatoid arthritis (RA) model and tracking of granulocytic-MDSCs (G-MDSCs) in vivo using Positron Emission Tomography/Magnet Resonance Imaging (PET/MRI)

Conference Series LLC Joint International Event on 5^th European Immunology & Innate Immunity

July 21-23, 2016 Berlin, Germany

Kerstin Fuchs, Hasan-halit Oez, Melanie Carevic, Natalie Altmeyer, Dominik Hartl, Bernd J Pichler and Manfred Kneilling

Eberhard Karls University Tubingen, Germany

Posters & Accepted Abstracts: J Clin Cell Immunol

Abstract :

Monocytic MDSCs (M-MDSC) and G-MDSCs are immature myeloid cells (CD11b+ Gr1+) and important regulators of basic immune responses. To date the role of MDSCs during RA is quite unknown; hence the aim of this study was to analyze the occurrence and homing of MDSCs during the effector phase in the GPI-serum RA mouse model. Further, we aimed to track 64Cu-PTSM or 64Cu-1A8 labeled G-MDSC after I.V. injection in RA mice by PET/MRI in vivo. BALB/c mice were injected with GPI-Ab to induce RA. We isolated cells from lavage of RA and healthy ankles at days 1, 3 and 6 and performed FACS analysis to identify G-MDSCs (Ly6G+) and M-MDSCs (Ly6C+). Ly6G antibody (Ab) or isotype Ab were used to deplete G-MDSCs. We labeled G-MDSCs intracellular with 64Cu-PTSM or Ly6G-Ab (1A8) 64Cu-1A8. Labeled cells were I.V. injected in RA mice on day 6 and tracked their homing patterns by PET/MRI. On day 1 less than 10%, day 3 up to 55% and day 6 up to 70% of infiltrating CD11b+ cells were identified as G-MDSCs. Contrary the expression of M-MDSCs in arthritic ankle lavage was not affected. G-MDSC depletion with Ly6G Ab on day 6 after RA induction reduced the number of GMDSC to less than 10%. In vivo 64Cu-PTSM-G-MDSCs from RA ankles homed to arthritic ankles 1 hour post injection (5.5���±0.6 % ID/cc) and 3.9���±0.5% ID/cc after 24 hours. In contrast 64Cu 1A8-G-MDSCs showed enhanced homing into GPI-arthritic ankles (1 hour: 7.2%���±3.0% ID/cc; 24 hours: 7.7���±2.6% ID/cc) compared to 64Cu-PTSM-G-MDSCs. Thus, our data indicate that most of the infiltrating cells in inflamed ankles are G-MDSCs and depletion of Ly6G+ cells lead to a massive decrease of G-MDSCs and arthritic joint inflammation, indicating a new therapeutic approach. 64Cu-1A8G cell labeling showed promising results for tracking G-MDSCs in vivo.