T-cells dysregulate hematopoiesis in Myeloproliferative Neoplasm through increased interferon-gamma production
العنوان: | T-cells dysregulate hematopoiesis in Myeloproliferative Neoplasm through increased interferon-gamma production |
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المؤلفون: | Hew Yeng Lai, Gajalakshmi Ramanathan, Stefan Brooks, Brianna Craver, Angela Fleischman |
المصدر: | The Journal of Immunology. 204:145.30-145.30 |
بيانات النشر: | The American Association of Immunologists, 2020. |
سنة النشر: | 2020 |
مصطلحات موضوعية: | Immunology, Immunology and Allergy |
الوصف: | Chronic inflammation is a key feature of myeloproliferative neoplasm (MPN), a hematological malignancy. MPN is characterized acquisition of a somatic mutation in hematopoietic stem cells, most commonly the JAK2V617F mutation, which leads to unrestrained expansion of myeloid cells. Although lymphoid compartments do not have the JAK2V617F mutation, these cells are key mediators of inflammation. The precise role of lymphoid cells in disease pathogenesis is unclear. We found that CD4+ T cells from MPN patients produce significantly more interferon gamma (IFNg) than normal CD4+ T cells. IFNg has been reported to suppress the growth of myeloid colonies. We found that removal of T cells from peripheral blood mononuclear cells of MPN patients enhance myeloid colony formation. Removal of T cell also increase fraction of wild-type myeloid colonies, demonstrating that wild-type cells are more sensitive to suppression by T cells. In addition, MPN mouse model using transduction-transplantation of JAK2V617F in RAG2−/− mice, lacking in T and B cells, display an attenuated MPN phenotype. Moreover, transplantation of JAK2V617F RAG2−/− bone marrow with wild-type bone marrow into lethally irradiated wild-type recipient restored the MPN pathology, such as erythrocytosis and expansion of megakaryocytes. This implicates that lymphocytes play an important role in driving MPN pathogenesis. More importantly, inhibition of T cells in JAK2V617F transplanted mouse using cyclosporine attenuates spleen size and marrow fibrosis, demonstrating that suppression of T cells after disease has already been established is therapeutic. In sum, these data shows that T mediates pathogenesis in MPN, and that suppressing T cells in MPN may have therapeutic benefit. |
تدمد: | 1550-6606 0022-1767 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::c6fba632efd76fdcbf837b0ecf17b796 https://doi.org/10.4049/jimmunol.204.supp.145.30 |
رقم الأكسشن: | edsair.doi...........c6fba632efd76fdcbf837b0ecf17b796 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15506606 00221767 |
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