Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8739541 | Journal of Autoimmunity | 2018 | 11 Pages |
Abstract
Myelofibrosis usually occurs either as a part of a myelodysplastic syndrome or in conjunction with neoplasia. It is not commonly thought of an autoimmune disease. We reported that p40â/âIL-2Rαâ/â (interleukin-12p40 and interleukin-2 receptor alpha double knockout) mice, a mouse model of human primary biliary cholangitis, exhibited features consistent with autoimmune myelofibrosis, including anemia associated with bone marrow fibrosis, and extramedullary hematopoiesis (EMH) including LSK (Lineage-c-Kit+Sca-1+) cells in spleen, liver and peripheral blood. There were also increased LSK cells in bone marrow but they demonstrated impaired hematopoiesis. Importantly effector memory T cells that infiltrated the bone marrow of p40â/âIL-2Rαâ/â mice manifested a higher ability to produce IFN-γ. CD8+ T cells, already known to play a dominate role in portal inflammation, were also key for bone marrow dysregulation and EMH. IFN-γ was the key cytokine that induced bone marrow fibrosis, bone marrow failure and EMH. Finally anti-CD8α antibody therapy fully protected p40â/âIL-2Rαâ/â mice from autoimmune myelofibrosis. In conclusion, our results demonstrate that CD8+ T cells and IFN-γ are associated with autoimmune myelofibrosis, a finding that may allow targeting of CD8+ T cells and IFN-γ as a therapeutic targets.
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Authors
Yuan Yao, Liang Li, Shu-Han Yang, Cai-Yue Gao, Liang-Huan Liao, Yu-Qing Xie, Xue-Ying Yin, Yan-Qing Yang, Yun-Yun Fei, Zhe-Xiong Lian,