BACH2 restricts NK cell maturation and function, limiting immunity to cancer metastasis.
BACH2 restricts NK cell maturation and function, limiting immunity to cancer metastasis.
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DOI：
10.1084/jem.20211476
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发表时间：
2022-12-05
影响因子：
15.3
通讯作者：
Roychoudhuri, Rahul
中科院分区：
文献类型：
--
作者：
Imianowski, Charlotte J.;Whiteside, Sarah K.;Lozano, Teresa;Evans, Alexander C.;Benson, Jayme D.;Courreges, Christina J. F.;Sadiyah, Firas;Lau, Colleen M.;Zandhuis, Nordin D.;Grant, Francis M.;Schuijs, Martijn J.;Vardaka, Panagiota;Kuo, Paula;Soilleux, Elizabeth J.;Yang, Jie;Sun, Joseph C.;Kurosaki, Tomohiro;Okkenhaug, Klaus;Halim, Timotheus Y. F.;Roychoudhuri, Rahul
NK细胞在免疫监视中起着关键作用，但其成熟和功能的负调节因子的特征很差。Imianowski等人表明，转录抑制因子BACH2限制NK细胞成熟和抗肿瘤功能，对免疫系统发育有影响。自然杀伤（NK）细胞对免疫监视感染和癌症至关重要。它们在免疫监视中的作用要求NK细胞以静止状态存在于组织内。NK细胞在组织中保持静止的机制尚未完全阐明。转录抑制因子BACH2在适应性免疫系统中起着关键作用，但其在先天淋巴细胞中的功能尚不清楚。在这里，我们表明，BACH 2作为一个内在的负调节NK细胞的成熟和功能。BACH 2在发育和成熟的NK细胞内表达，并通过在弱刺激信号存在下限制其成熟来促进未成熟NK细胞的维持。NK细胞内BACH 2的缺失导致具有不受限制的细胞毒性功能的活化NK细胞在组织内积累，其介导对肺癌转移的增强的免疫监视。这些发现确立了BACH 2作为天然细胞毒性功能和NK细胞肿瘤免疫监视的全球负调节因子的关键功能。
NK cells play a critical role in immune surveillance, yet negative regulators of their maturation and function are poorly characterized. Imianowski et al. show that the transcriptional repressor BACH2 restricts NK cell maturation and anti-tumor function, with implications for immunotherapeutic development. Natural killer (NK) cells are critical to immune surveillance against infections and cancer. Their role in immune surveillance requires that NK cells are present within tissues in a quiescent state. Mechanisms by which NK cells remain quiescent in tissues are incompletely elucidated. The transcriptional repressor BACH2 plays a critical role within the adaptive immune system, but its function within innate lymphocytes has been unclear. Here, we show that BACH2 acts as an intrinsic negative regulator of NK cell maturation and function. BACH2 is expressed within developing and mature NK cells and promotes the maintenance of immature NK cells by restricting their maturation in the presence of weak stimulatory signals. Loss of BACH2 within NK cells results in accumulation of activated NK cells with unrestrained cytotoxic function within tissues, which mediate augmented immune surveillance to pulmonary cancer metastasis. These findings establish a critical function of BACH2 as a global negative regulator of innate cytotoxic function and tumor immune surveillance by NK cells.
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影响因子：
64.5
作者：
Litchfield K;Reading JL;Puttick C;Thakkar K;Abbosh C;Bentham R;Watkins TBK;Rosenthal R;Biswas D;Rowan A;Lim E;Al Bakir M;Turati V;Guerra-Assunção JA;Conde L;Furness AJS;Saini SK;Hadrup SR;Herrero J;Lee SH;Van Loo P;Enver T;Larkin J;Hellmann MD;Turajlic S;Quezada SA;McGranahan N;Swanton C
通讯作者：
Swanton C
影响因子：
30.5
作者：
Lau CM;Adams NM;Geary CD;Weizman OE;Rapp M;Pritykin Y;Leslie CS;Sun JC
通讯作者：
Sun JC
影响因子：
30.5
作者：
Afzali B;Grönholm J;Vandrovcova J;O'Brien C;Sun HW;Vanderleyden I;Davis FP;Khoder A;Zhang Y;Hegazy AN;Villarino AV;Palmer IW;Kaufman J;Watts NR;Kazemian M;Kamenyeva O;Keith J;Sayed A;Kasperaviciute D;Mueller M;Hughes JD;Fuss IJ;Sadiyah MF;Montgomery-Recht K;McElwee J;Restifo NP;Strober W;Linterman MA;Wingfield PT;Uhlig HH;Roychoudhuri R;Aitman TJ;Kelleher P;Lenardo MJ;O'Shea JJ;Cooper N;Laurence ADJ
通讯作者：
Laurence ADJ
影响因子：
32.4
作者：
Herndler-Brandstetter D;Ishigame H;Shinnakasu R;Plajer V;Stecher C;Zhao J;Lietzenmayer M;Kroehling L;Takumi A;Kometani K;Inoue T;Kluger Y;Kaech SM;Kurosaki T;Okada T;Flavell RA
通讯作者：
Flavell RA
影响因子：
7
作者：
Geiger TL;Sun JC
通讯作者：
Sun JC