2016 Fiscal Year Final Research Report
Identification of GATA2 function in dendritic cell differentiation for elucidating the pathological mechanism of MonoMAC syndrome
| Project/Area Number |
26860716
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
|
|---|
| Research Collaborator |
Onodera Koichi 東北大学, 大学院医学系研究科・血液免疫病学分野 (80792291)
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Keywords | GATA2 / MonoMAC症候群 / 樹状細胞 / 転写因子 |
|---|
| Outline of Final Research Achievements |
Mutations in GATA2 are associated with the monocytopenia and mycobacterial infection (MonoMAC) syndrome. In this syndrome, monocyte, B-cell, NK-cell, and dendritic cell (DC) populations are diminished or undetectable. DCs are central regulators for immune response. We investigated the role of GATA2 in DC differentiation and function by Gata2 conditional knockout mice. It was found that GATA2 was required for the in vitro generation of DCs from common myeloid-restricted progenitors and common DC precursors. But common lymphoid-restricted progenitors or granulocyte-macrophage progenitors were not affected for the DC differentiation by GATA2-knockout. Moreover, expression profiling showed GATA2 could suppress T-cell-related genes, including Gata3 and Tcf7 in myeloid progenitors. These findings suggest GATA2 has an important role in cell-fate specification toward the myeloid vs. T-cell lineage by regulating lineage-specific transcription factors in progenitors.
|
| Free Research Field |
血液内科学
|
