Identification of novel microRNA signatures linked to acquired aplastic anemia.
Emerging evidence indicates that microRNA control and modulate immunity. MicroRNA have not been investigated in acquired aplastic anemia, a T-cell-mediated immune disease. Analysis of 84 microRNA expression levels in CD4(+) and CD8(+) T cells of patients with aplastic anemia revealed concurrent down-regulation of miR-126-3p, miR-145-5p, miR-223-3p, and miR-199a-5p (>3-fold change, P<0.05) in both T-cell populations, which were unique in aplastic anemia compared to other hematologic disorders. MiR-126-3p and miR-223-3p were down-regulated in CD4(+) T effector memory cells, and miR-126-3p, miR-145-5p, and miR-223-3p were down-regulated in CD8(+) T effector memory and terminal effector cells. Successful immunosuppressive therapy was associated with restoration to normal expression levels of miR-126-3p, miR-145-5p, and miR-223-3p (>2-fold change, P<0.05). In CD4(+) and CD8(+) T cells in aplastic anemia patients, MYC and PIK3R2 were up-regulated and proved to be targets of miR-145-5p and miR-126-3p, respectively. MiR-126-3p and miR-145-5p knockdown promoted proliferation and increased interferon-γ and granzyme B production in both CD4(+) and CD8(+) T cells. Our work describes previously unknown regulatory roles of microRNA in T-cell activation in aplastic anemia, which may open a new perspective for development of effective therapy. Clinicaltrials.gov identifier: NCT 01623167.
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA kohei.hosokawa@nih.gov.
Kohei
K
Hosokawa
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
Pawel
P
Muranski
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
Xingmin
X
Feng
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
Keyvan
K
Keyvanfar
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
Danielle M
DM
Townsley
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
Bogdan
B
Dumitriu
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
Jichun
J
Chen
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
Sachiko
S
Kajigaya
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
James G
JG
Taylor
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
Christopher S
CS
Hourigan
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
A John
AJ
Barrett
Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
Neal S
NS
Young
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D035683:MicroRNAs / Q000276:immunology*; D008875:Middle Aged
D035683:MicroRNAs