The microRNA cluster miR-17∼92 promotes TFH cell differentiation and represses subset-inappropriate gene expression.
The microRNA cluster miR-17∼92 promotes TFH cell differentiation and represses subset-inappropriate gene expression.
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T滤泡辅助性（TFH）细胞是典型的辅助性T细胞亚群，其专门使B细胞能够形成生发中心并产生高亲和力抗体。我们发现T细胞的微小RNA（miRNA）表达对TFH细胞分化至关重要。更具体地说，我们表明在蛋白质免疫后，微小RNA簇miR - 17~92以细胞内在的方式对强健的TFH细胞分化和功能至关重要，这种方式的发生与增殖变化无关。在病毒感染模型中，miR - 17~92抑制了TFH亚群不适当基因的表达，包括直接靶标视黄酸受体相关孤儿受体α（Rora）。基因敲除一个Rora等位基因可部分挽救miR - 17~92缺陷型TFH细胞中不适当的基因特征。我们的研究结果确定miR - 17~92簇是T细胞依赖性抗体应答、TFH细胞分化以及TFH细胞基因表达程序准确性的关键调节因子。
T follicular helper (TFH) cells are the prototypic helper T cell subset specialized to enable B cells to form germinal centers and produce high-affinity antibodies. We found that miRNA expression by T cells was essential for TFH cell differentiation. More specifically, we show that after protein immunization the microRNA cluster miR-17~92 was critical for robust TFH cell differentiation and function in a cell-intrinsic manner that occurred regardless of changes in proliferation. In a viral infection model, miR-17~92 restrained the expression of TFH subset-inappropriate genes, including the direct target RAR-related orphan receptor alpha (Rora). Genetically removing one Rora allele partially rescued the inappropriate gene signature in miR-17~92-deficient TFH cells. Our results identify the miR-17~92 cluster as a critical regulator of T cell-dependent antibody responses, TFH cell differentiation and the fidelity of the TFH cell gene expression program.
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DOI：
10.1084/jem.20120994
发表时间：
2012-07-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ma CS;Deenick EK;Batten M;Tangye SG
通讯作者：
Tangye SG
DOI：
10.1126/science.1176676
发表时间：
2009-08-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Nurieva RI;Chung Y;Martinez GJ;Yang XO;Tanaka S;Matskevitch TD;Wang YH;Dong C
通讯作者：
Dong C
影响因子：
20.3
作者：
Jiang, Shan;Li, Chaoran;Li, Qi-Jing
通讯作者：
Li, Qi-Jing
影响因子：
32.4
作者：
Nakayamada S;Kanno Y;Takahashi H;Jankovic D;Lu KT;Johnson TA;Sun HW;Vahedi G;Hakim O;Handon R;Schwartzberg PL;Hager GL;O'Shea JJ
通讯作者：
O'Shea JJ
DOI：
10.1084/jem.20111174
发表时间：
2012-02-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Johnston RJ;Choi YS;Diamond JA;Yang JA;Crotty S
通讯作者：
Crotty S