The microRNA cluster miR-17∼92 promotes TFH cell differentiation and represses subset-inappropriate gene expression

被引：172

作者：

Baumjohann, Dirk ^{[1
]}

Kageyama, Robin ^{[1
]}

Clingan, Jonathan M. ^{[2
,3
,4
]}

Morar, Malika M. ^{[5
,6
]}

Patel, Sana ^{[1
]}

de Kouchkovsky, Dimitri ^{[5
,6
]}

Bannard, Oliver ^{[7
]}

Bluestone, Jeffrey A. ^{[5
,6
,8
]}

Matloubian, Mehrdad ^{[2
,3
]}

Ansel, K. Mark ^{[1
]}

Jeker, Lukas T. ^{[5
,6
,8
]}

机构：

[1] Univ Calif San Francisco, Dept Microbiol & Immunol, Sandler Asthma Basic Res Ctr, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Div Rheumatol, Dept Med, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Grad Program Biomed Sci, San Francisco, CA 94143 USA

[5] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[7] Univ Calif San Francisco, Dept Microbiol & Immunol, Howard Hughes Med Inst, San Francisco, CA 94143 USA

[8] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 08期

基金：

瑞士国家科学基金会; 英国惠康基金; 美国国家科学基金会; 美国国家卫生研究院;

关键词：

CUTTING EDGE; BCL6; PLASTICITY; RESPONSES; EFFECTOR; ROBUSTNESS; REGULATORS; SIGNALS; TARGETS; ANTIGEN;

D O I：

10.1038/ni.2642

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Follicular helper T cells (T-FH cells) are the prototypic helper T cell subset specialized to enable B cells to form germinal centers (GCs) and produce high-affinity antibodies. We found that expression of microRNAs (miRNAs) by T cells was essential for T-FH cell differentiation. More specifically, we show that after immunization of mice with protein, the miRNA cluster miR-17 similar to 92 was critical for robust differentiation and function of T-FH cells in a cell-intrinsic manner that occurred regardless of changes in proliferation. In a viral infection model, miR-17 similar to 92 restrained the expression of genes 'inappropriate' to the T-FH cell subset, including the direct miR-17 similar to 92 target Rora. Removal of one Rora allele partially 'rescued' the inappropriate gene signature in miR-17 similar to 92-deficient T-FH cells. Our results identify the miR-17 similar to 92 cluster as a critical regulator of T cell-dependent antibody responses, TFH cell differentiation and the fidelity of the T-FH cell gene-expression program.

引用

页码：840 / +

页数：11

共 53 条

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