The microRNA cluster miR-17∼92 promotes TFH cell differentiation and represses subset-inappropriate gene expression.
Dirk BaumjohannRobin KageyamaJonathan M ClinganMalika M MorarSana PatelDimitri de KouchkovskyOliver BannardJeffrey A BluestoneMehrdad MatloubianK Mark AnselLukas T JekerPublished in: Nature immunology (2013)
Follicular helper T cells (TFH 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 TFH cell differentiation. More specifically, we show that after immunization of mice with protein, the miRNA cluster miR-17∼92 was critical for robust differentiation and function of TFH cells in a cell-intrinsic manner that occurred regardless of changes in proliferation. In a viral infection model, miR-17∼92 restrained the expression of genes 'inappropriate' to the TFH cell subset, including the direct miR-17∼92 target Rora. Removal of 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.
Keyphrases
- cell proliferation
- long non coding rna
- gene expression
- long noncoding rna
- poor prognosis
- induced apoptosis
- cell cycle arrest
- single cell
- dna methylation
- cell therapy
- stem cells
- transcription factor
- endoplasmic reticulum stress
- binding protein
- immune response
- bone marrow
- quality improvement
- adipose tissue
- wild type
- genome wide analysis