LRRC25 plays a key role in all-trans retinoic acid-induced granulocytic differentiation as a novel potential leukocyte differentiation antigen.
10.1007/s13238-017-0421-7
- Author:
Weili LIU
1
;
Ting LI
1
;
Pingzhang WANG
1
;
Wanchang LIU
1
;
Fujun LIU
1
;
Xiaoning MO
1
;
Zhengyang LIU
1
;
Quansheng SONG
1
;
Ping LV
1
;
Guorui RUAN
2
;
Wenling HAN
3
Author Information
1. Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology (Ministry of Health), Peking University Health Science Center, Beijing, 100191, China.
2. Institute of Hematology, Peking University People's Hospital, Beijing, 100044, China.
3. Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology (Ministry of Health), Peking University Health Science Center, Beijing, 100191, China. hanwl@bjmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
AML;
ATRA;
LRRC25;
differentiation antigen;
granulocytic differentiation
- MeSH:
Antigens, Differentiation;
immunology;
metabolism;
Cell Differentiation;
drug effects;
Cell Line, Tumor;
Granulocytes;
cytology;
drug effects;
immunology;
metabolism;
Humans;
Leukocytes;
cytology;
drug effects;
immunology;
metabolism;
Membrane Proteins;
antagonists & inhibitors;
immunology;
metabolism;
RNA, Small Interfering;
pharmacology;
Tretinoin;
pharmacology
- From:
Protein & Cell
2018;9(9):785-798
- CountryChina
- Language:English
-
Abstract:
Leukocyte differentiation antigens (LDAs) play important roles in the immune system, by serving as surface markers and participating in multiple biological activities, such as recognizing pathogens, mediating membrane signals, interacting with other cells or systems, and regulating cell differentiation and activation. Data mining is a powerful tool used to identify novel LDAs from whole genome. LRRC25 (leucine rich repeat-containing 25) was predicted to have a role in the function of myeloid cells by a large-scale "omics" data analysis. Further experimental validation showed that LRRC25 is highly expressed in primary myeloid cells, such as granulocytes and monocytes, and lowly/intermediately expressed in B cells, but not in T cells and almost all NK cells. It was down-regulated in multiple acute myeloid leukemia (AML) cell lines and bone marrow cells of AML patients and up-regulated after all-trans retinoic acid (ATRA)-mediated granulocytic differentiation in AML cell lines and acute promyelocytic leukemia (APL; AML-M3, FAB classification) cells. Localization analysis showed that LRRC25 is a type I transmembrane molecule. Although ectopic LRRC25 did not promote spontaneous differentiation of NB4 cells, knockdown of LRRC25 by siRNA or shRNA and knockout of LRRC25 by the CRISPR-Cas9 system attenuated ATRA-induced terminal granulocytic differentiation, and restoration of LRRC25 in knockout cells could rescue ATRA-induced granulocytic differentiation. Therefore, LRRC25, a potential leukocyte differentiation antigen, is a key regulator of ATRA-induced granulocytic differentiation.
