SatM Involved in Chronic Gvhd after Bone Marrow Transplantation.

Abstract

Background GVHD is a result of immune attack of host tissues, such as the skin, gut, liver, and lung, by various immune cells in hematopoietic stem cell transplantation (HSCT). Chronic GVHD (cGVHD) is the main cause of late death and morbidity after allogeneic HSCT. Fibrosis constitutes the end stage of the inflammatory process in cGVHD leading to major morbidity. Recently, segregated-nucleus-containing atypical monocytes (SatM) that involved in lung fibrosis has been identified. We hypothesized that SatM involved in tissue fibrosis of chronic GVHD after bone marrow transplantation. Materials and Methods Lung cGVHD model: B10.BR mice received were conditioned with Cyclophosphamide (120mg/kg/day, intraperitoneally, day-3 and -2) and TBI (8.3Gy, day-1), followed by infusion of 10•∼106 C57BL/6j T cell–depleted BM (TCD-BM) plus 60000 purified splenic T cell. Respiratory function test and flowcytometry of BALF were analyzed at BMT day56. Sclerodermatous cGVHD model: BALB/c mice received a single dose of 5.8 Gy x-ray total body irradiation. Recipient mice were injected with 2•∼106 purified splenic T cells and 8•∼106 TCD-BM cells from B10.D2 donors. Donor cells were injected intravenously into the recipients on day 0. The SatM in the skin and the spleen are analyzed by flow cytometry at BMT day28. Results Compared to syngeneic group of the lung cGVHD model, allogeneic recipient developed fibrosis around the bronchi. In the respiratory function test, allogeneic recipient showed higher respiratory resistance. No difference was observed in the number of splenic monocytes by flowcytometry. However, Ly6clow monocyte, Ly6c+ monocyte and SatM increased in BALF of allogeneic recipient. In the sclerodermatous cGVHD model, SatM increased in ear of allogeneic recipient but not in spleen ( Figure 1 ). Discussion In this study, SatM observed in tissues targeted by cGVHD, but not in spleen. This result may indicate that SatM involved in fibrosis of cGVHD model. To demonstrate that SatM causes the fibrosis of cGVHD, we currently establish cGVHD model with SatM deficiency mouse (Cebpb−/− mouse).