RIG-I plays a critical role in negatively regulating granulocytic proliferation.
RIG-I has been implicated in innate immunity by sensing intracellular viral RNAs and inducing type I IFN production. However, we have found a significant RIG-I induction in a biological setting without active viral infection-namely, during RA-induced terminal granulocytic differentiation of acute myeloid leukemias. Here, we present evidence that a significant Rig-I induction also occurs during normal myelopoiesis and that the disruption of the Rig-I gene in mice leads to the development of a progressive myeloproliferative disorder. The initiation of progressive myeloproliferative disorder is mainly due to an intrinsic defect of Rig-I(-/-) myeloid cells, which are characterized by a reduced expression of IFN consensus sequence binding protein, a major regulator of myeloid differentiation. Thus, our study reveals a critical regulatory role of Rig-I in modulating the generation and differentiation of granulocytes.
Zhang
Nan-Nan
NN
State Key Laboratory for Medical Genomics, Institute of Health Science, Shanghai Institute for Biological Sciences and Graduate School, Chinese Academy of Sciences, People's Republic of China.
Shen
Shu-Hong
SH
Jiang
Lin-Jia
LJ
Zhang
Wu
W
Zhang
Hong-Xin
HX
Sun
Yue-Ping
YP
Li
Xian-Yang
XY
Huang
Qiu-Hua
QH
Ge
Bao-Xue
BX
Chen
Sai-Juan
SJ
Wang
Zhu-Gang
ZG
Chen
Zhu
Z
Zhu
Jiang
J
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D005091:Exons; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology; D009196:Myeloproliferative Disorders / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000502:physiology*
C437968:PLAAT4 protein, human; D018168:Receptors, Retinoic Acid; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases