Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Fibrosis is the end-result of most inflammatory conditions, but its pathogenesis remains unclear. Studies in patients and animal models suggest a role for T-cells and innate immune cells including dendritic cells (DC) in the development of fibrosis. DCs play a role in T-cell priming and differentiation also infiltrate the lung in response to bleomycin injection in animals. DCs also accumulate in lungs of patients with idiopathic pulmonary fibrosis and in skin of patients with systemic sclerosis (SSc) . However, the exact role of DCs in the pathogenesis of fibrotic diseases including SSc is unclear. We investigated the role of plasmacytoid dendritic cells (pDC) in the pathogenesis of systemic fibrosis using the bleomycin model and clinical samples from patients with systemic sclerosis (SSc).
Female C57BL/6 mice were depleted of pDCs using anti-pDCA1 and were compared to mice depleted with isotype control IgG2b. clinical observation and analyses were carried of draining LN, spleen, lungs and skin including flow cytometry, pathology, collagen production and RT PCR array. In our work, we evaluated human data (HRCT and BAL) from SSc Imatinib trial. We also examined pDCs in Peripheral blood, skin and lung in controls as well as SSc patients.
pDCs were more profoundly increased than other immune cells in the lung and lung-draining lymph nodes, but not in the spleen, of bleomycin-injected mice compared to control animals. Depletion of pDCs improved the clinical score, lung histopathology score, skin thickness, and collagen content compared to control antibody-treated animals. B-cells, T-cells and natural killer T-cells were reduced in the lungs, but unaffected/increased in the spleen, of pDC-depleted mice as compared to controls. pDC-depleted mice also had a reduced expression of genes involved in chemotaxis, dendritic cell differentiation, inflammation, and fibrosis in the lungs as compared to controls. In humans, while pDCs were reduced in the peripheral blood of patients with SSc compared to healthy donors, their numbers were increased in the lung and skin of patients with SSc. The frequencies of pDCs in the bronchoalveolar lavage (BAL) correlated with SSc-lung disease scores and with IL-4+ and CD4+ T-cells in BAL.
Taken together, our observations identify the increased trafficking to pDCs to the affected organs as a potential therapeutic target in fibrotic diseases.
To cite this abstract in AMA style:Kafaja S, Valera I, Divekar A, Saggar R, Khanna D, Furst DE, Singh RR. Plasmacytoid Dendritic Cells in Systemic Fibrosis: Pathogenic Role in Bleomycin-Induced Fibrosis Model and Correlation with Disease in Patients with Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/plasmacytoid-dendritic-cells-in-systemic-fibrosis-pathogenic-role-in-bleomycin-induced-fibrosis-model-and-correlation-with-disease-in-patients-with-systemic-sclerosis/. Accessed October 4, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/plasmacytoid-dendritic-cells-in-systemic-fibrosis-pathogenic-role-in-bleomycin-induced-fibrosis-model-and-correlation-with-disease-in-patients-with-systemic-sclerosis/