학술논문
MiR-23~27~24-mediated control of humoral immunity reveals a TOX-driven regulatory circuit in follicular helper T cell differentiation.
Document Type
article
Author
Wu, Cheng-Jang; Cho, Sunglim; Huang, Hsi-Yuan; Lu, Chun-Hao; Russ, Jasmin; Cruz, Leilani; da Cunha, Flavia; Chen, Mei-Chi; Lin, Ling-Li; Warner, Lindsey; Liao, Hsin-Kai; Utzschneider, Daniel; Quon, Sara; Berner, Jacqueline; Camara, Niels; Zehn, Dietmar; Belmonte, Juan; Chen, Li-Chen; Huang, Shiang-Fu; Kuo, Ming-Ling; Lu, Li-Fan
Source
Science Advances. 5(12)
Subject
Language
Abstract
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.