Immune regulatory effects of microRNA9-3

Danfeng Lin; Yongguang Zhang; Dongya Cui; Jianhui Wei; Yawen Chen; Jinfeng Chen; Shan Xu; Dongyue Zhao; Qi Chen

doi:10.1016/j.bcmd.2022.102697

Immune regulatory effects of microRNA9-3

Blood Cells Mol Dis. 2022 Nov:97:102697. doi: 10.1016/j.bcmd.2022.102697. Epub 2022 Jul 19.

Authors

Danfeng Lin¹, Yongguang Zhang¹, Dongya Cui¹, Jianhui Wei¹, Yawen Chen¹, Jinfeng Chen¹, Shan Xu¹, Dongyue Zhao¹, Qi Chen²

Affiliations

¹ Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University Qishan Campus, Fuzhou, Fujian Province 350117, China.
² Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University Qishan Campus, Fuzhou, Fujian Province 350117, China. Electronic address: chenqi@fjnu.edu.cn.

PMID: 35872110
DOI: 10.1016/j.bcmd.2022.102697

Abstract

MicroRNAs are known to regulate cell proliferation, differentiation, and apoptosis. However, the immunological mechanism and role of microRNA9-3 (miR9-3) are unknown. This study used CRISPR/cas9 technology to knock out miR9-3 to modulate its expression level. FACS results showed that the absolute number of total B cells declined in miR9-3-deficiency in the spleen (Sp), bone marrow (BM), and lymph node (LN) to different levels compared to the wild-type. Also, the absolute numbers of Fo, T1, and T2 cells decreased both in Sp and LN. The absolute numbers of total T cells in Sp and LN declined sharply; CD4⁺ and CD8⁺ T cells showed a dramatic decrease in Sp, LN, and Th (thymus) of the miR9-3^- group. In BM, the cells number of immature B cells, pro-pre-B cells, pro-B cells, and pre-B cells reduced to different levels, while mature B cells were comparable to wild-type. These data illustrated that miR9-3-deficiency impaired the development of B cells in BM. Also, the development of T cells was severely impaired. In Th, the numbers of DN and DP cells were remarkably reduced in the miR9-3 mutant mice. Also, the numbers of DN-1, DN-3, and DN-4 cells decreased. The absolute number of cells in the hematopoietic stem cell (HSC) system such as LT-HSC (long-term HSC), ST-HSC (short-term HSC), MPP (multipotent progenitor), GMP (granulocyte-macrophage progenitor), CMP (common myeloid progenitors), MEP (megakaryocyte-erythroid progenitor), and CLP (common lymphoid progenitor) all were decreased in miR9-3 deficient mice. These results showed that miR9-3 deficiency initiated the damage to the entire hematopoietic system. Moreover, the absolute number of myeloid cells in both Sp and BM decreased in mutant mice. The cells number of NK cells showed a sharp reduction in Sp whereas the change was not significant in BM. The above results suggest that miR9-3 participates in the immune regulation of B cells, T cells, and the HSC system, highlighting its regulatory roles.

Keywords: B cell; Bone marrow; HSC; Lymph node; Spleen; T cell; Thymus; miR9-3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
B-Lymphocytes*
Bone Marrow / pathology
Bone Marrow Cells
CD4-Positive T-Lymphocytes*
CD8-Positive T-Lymphocytes*
Cell Differentiation
Hematopoietic Stem Cells* / metabolism
Mice
Mice, Inbred C57BL
MicroRNAs* / immunology

Substances

MIRN9 microRNA, mouse
MicroRNAs