CD8+ T cells and IFN-γ induce autoimmune myelofibrosis in mice

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 p40−/−IL-2Rα−/− (interleukin-12p40 and interleukin-2 receptor alpha double knockout) mice, a mouse model of human primar...

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Published in:Journal of autoimmunity 2018-05, Vol.89, p.101-111
Main Authors: Yao, Yuan, Li, Liang, Yang, Shu-Han, Gao, Cai-Yue, Liao, Liang-Huan, Xie, Yu-Qing, Yin, Xue-Ying, Yang, Yan-Qing, Fei, Yun-Yun, Lian, Zhe-Xiong
Format: Article
Language:English
Subjects:
Autoimmune myelofibrosis
Bone marrow T cells
CD8+ T cells
Extramedullary hematopoiesis
IFN-γ
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Summary: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 p40−/−IL-2Rα−/− (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 p40−/−IL-2Rα−/− 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 p40−/−IL-2Rα−/− 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. •p40−/−IL-2Rα−/− mice displayed anemia and extramedullary hematopoiesis.•p40−/−IL-2Rα−/− mice had myelofibrosis with increased IFN-γ producing T cells.•CD8+ T cells and IFN-γ promoted the development of autoimmune myelofibrosis.•Depletion of CD8+ T cells successfully ameliorated autoimmune myelofibrosis.
ISSN:0896-8411
1095-9157
DOI:10.1016/j.jaut.2017.12.011