Regulation of inflammation by SOCS1 and SOCS3 in the syngeneic bone marrow transplantation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K19547
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Niigata University
• Principal Investigator: Ushiki Takashi 新潟大学, 医歯学総合病院, 講師 (80579152)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: SOCS1 / SOCS3 / 慢性炎症 / 遺伝子間相互作用 / 骨髄移植

Outline of Final Research Achievements

Combined hematopoietic loss of SOCS1 and SOCS3 causes rapid inflammatory disease in the syngeneic bone marrow transplantation. Loss of SOCS1 increases the number of CD8+CD44high cells. The expression of homing markers on these T cells may facilitate migration to organs and tissues, and the propensity for production of pro-inflammatory cytokines and chemokines, such as RANTES, MIP1a, GM-CSF and IL-3 for recruiting myeloid cells, as well as development of high circulating G-CSF concentrations, can account for the pathological infiltration of neutrophils, monocytes, eosinophils and lymphocytes at the numerous sites of inflammation in SOCS1KO mice. Our data extend the model to suggest that the absence of SOCS3 in the already pro-inflammatory environment established by SOCS1 deficiency, results in hyper-responsiveness of immune cells to cytokines such as G-CSF and IL-6, and dramatically accelerates myeloid proliferation and inflammatory infiltration of target tissues.

Free Research Field

血液内科学