Date: Sunday, October 21, 2018
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Myeloid derived suppressor cells (MDSCs) are major T cell suppressors, and their dysfunction has been implicated in the pathophysiology of autoimmune diseases. MDSCs suppress T cells using multiple co-receptors including the DC-HIL receptor, which has been shown to be a major receptor in monocytic MDSCs (M-MDSCs). We previously showed that DC-HIL+ M-MDSCs from patients with psoriasis are expanded and functionally deficient, thus enhancing autoreactivity. However, the function of MDSCs in cutaneous lupus erythematosus (CLE) is poorly understood. We hypothesized that DC-HIL+ M-MDSCs are elevated in the peripheral blood and lesional skin of patients with CLE.
Methods: All patients were recruited through the UT Southwestern Cutaneous Lupus Registry. PBMCs from 20 CLE patients and 16 age- and gender-matched healthy controls were analyzed using flow cytometry. M-MDSCs were identified by the phenotype of CD14+ HLA-DRneg/low. To investigate the suppressor function of M-MDSCs, freshly isolated autologous M-MDSCs and T cells were co-cultured at varying ratios. T cell function was measured by secretion of IFN-γ by ELISA. Anti-DC-HIL mAb (50 μg/mL) was added to the 1:1 co-culture to study the role of the DC-HIL receptor. Immunohistochemical staining of five CLE lesional skin biopsies and three control skin biopsies using anti-DC-HIL antibodies was performed to study the population of MDSCs in skin tissue.
Results: CLE patients had significantly higher %M-MDSCs amongst PBMCs (2.3% (IQR: 1.2%-4.2%)) compared to controls (0.5% (0.1%-1.1%)) (p=0.0005). Percent DC-HIL+ M-MDSCs amongst PBMCs was also elevated in CLE patients (0.22% (0.06-0.67%)) compared to healthy controls (0.04% (0.01-0.1%)) (p=0.003). MDSCs isolated from PBMCs of three additional CLE patients suppressed activated autologous T cells in a dose-dependent manner. Addition of anti-DC-HIL monoclonal antibody partially reversed the suppressor function, indicating that DC-HIL is a receptor involved in MDSC-mediated T-cell suppression in CLE. Compared with normal skin, CLE skin had increased DC-HIL+ cells (p= 0.04), particularly at the dermal-epidermal junction. DC-HIL+ cells were in close proximity to CD3+ T cells at the dermal-epidermal junction, perifollicular, and perivascular areas.
Conclusion: In summary, DC-HIL+ M-MDSCs are expanded in CLE blood and skin, and display immunosuppressive properties. Their up-regulation in CLE blood may represent the body’s response to limiting disease severity, since most patients had mild disease activity. Further studies are needed to discern whether these cells help contain the immune dysregulation to skin, since few CLE patients progress to SLE.
To cite this abstract in AMA style:Florez-Pollack S, Tseng LC, Kobayashi M, Hosler G, Ariizumi K, Chong BF. DC-Hil+ Myeloid-Derived Suppressor Cells Are Elevated in the Peripheral Blood and Lesional Skin of Cutaneous Lupus Patients [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/dc-hil-myeloid-derived-suppressor-cells-are-elevated-in-the-peripheral-blood-and-lesional-skin-of-cutaneous-lupus-patients/. Accessed August 24, 2019.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dc-hil-myeloid-derived-suppressor-cells-are-elevated-in-the-peripheral-blood-and-lesional-skin-of-cutaneous-lupus-patients/