FTO negatively regulates the cytotoxic activity of natural killer cells

被引：21

作者：

Kim, Seok-Min ^{[1
,2
]}

Oh, Se-Chan ^{[1
,2
]}

Lee, Sun-Young ^{[1
,3
]}

Kong, Ling-Zu ^{[1
,4
]}

Lee, Jong-Hee ^{[2
,5
]}

Kim, Tae-Don ^{[1
,2
,6
,7
]}

机构：

[1] Korea Res Inst Biosci & Biotechnol KRIBB, Immunotherapy Res Ctr, Daejeon, South Korea

[2] Korea Univ Sci & Technol UST, KRIBB Sch Biosci, Dept Funct Genom, Daejeon, South Korea

[3] Korea Univ, Div Life Sci, Seoul, South Korea

[4] Chungnam Natl Univ, Dept Biochem, Daejeon, South Korea

[5] KRIBB, Natl Primate Res Ctr NPRC, Cheongju, South Korea

[6] Inst Basic Sci IBS, Biomed Math Grp, Daejeon, South Korea

[7] Sungkyunkwan Univ, Sch Pharm, Dept Biopharmaceut Convergence, Suwon, South Korea

来源：

EMBO REPORTS | 2023年 / 24卷 / 04期

基金：

新加坡国家研究基金会;

关键词：

epitranscriptome; FTO; m(6)A regulator; N6-methyladenosine; NK cell; MESSENGER-RNA METHYLATION; HEMATOPOIETIC STEM; FAT MASS; M(6)A; OBESITY; DEMETHYLASE; PROTEINS; GENE;

D O I：

10.15252/embr.202255681

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

N-6-Methyladenosine (m(6)A) is the most abundant epitranscriptomic mark and plays a fundamental role in almost every aspect of mRNA metabolism. Although m(6)A writers and readers have been widely studied, the roles of m(6)A erasers are not well-understood. Here, we investigate the role of FTO, one of the m(6)A erasers, in natural killer (NK) cell immunity. We observe that FTO-deficient NK cells are hyperactivated. Fto knockout (Fto(-/-)) mouse NK cells prevent melanoma metastasis in vivo, and FTO-deficient human NK cells enhance the antitumor response against leukemia in vitro. We find that FTO negatively regulates IL-2/15-driven JAK/STAT signaling by increasing the mRNA stability of suppressor of cytokine signaling protein (SOCS) family genes. Our results suggest that FTO is an essential modulator of NK cell immunity, providing a new immunotherapeutic strategy for allogeneic NK cell therapies.

引用

页数：15

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