| First Author | Wu CJ | Year | 2019 |
| Journal | Sci Adv | Volume | 5 |
| Issue | 12 | Pages | eaaw1715 |
| PubMed ID | 31844658 | Mgi Jnum | J:285440 |
| Mgi Id | MGI:6392984 | Doi | 10.1126/sciadv.aaw1715 |
| Citation | Wu CJ, et al. (2019) MiR-23~27~24-mediated control of humoral immunity reveals a TOX-driven regulatory circuit in follicular helper T cell differentiation. Sci Adv 5(12):eaaw1715 |
| abstractText | Follicular helper T (TFH) cells are essential for generating protective humoral immunity. To date, microRNAs (miRNAs) have emerged as important players in regulating TFH cell biology. Here, we show that loss of miR-23~27~24 clusters in T cells resulted in elevated TFH cell frequencies upon different immune challenges, whereas overexpression of this miRNA family led to reduced TFH cell responses. Mechanistically, miR-23~27~24 clusters coordinately control TFH cells through targeting a network of genes that are crucial for TFH cell biology. Among them, thymocyte selection-associated HMG-box protein (TOX) was identified as a central transcription regulator in TFH cell development. TOX is highly up-regulated in both mouse and human TFH cells in a BCL6-dependent manner. In turn, TOX promotes the expression of multiple molecules that play critical roles in TFH cell differentiation and function. Collectively, our results establish a key miRNA regulon that maintains optimal TFH cell responses for resultant humoral immunity. |
