MiR-23~27~24-mediated control of humoral immunity reveals a TOX-driven regulatory circuit in follicular helper T cell differentiation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31844658.
- Also identified by DOI 10.1126/sciadv.aaw1715 and PMC identifier 6905868.
- Licence recorded as CC BY-NC.
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Abstract
Follicular helper T (T<sub>FH</sub>) cells are essential for generating protective humoral immunity. To date, microRNAs (miRNAs) have emerged as important players in regulating T<sub>FH</sub> cell biology. Here, we show that loss of miR-23~27~24 clusters in T cells resulted in elevated T<sub>FH</sub> cell frequencies upon different immune challenges, whereas overexpression of this miRNA family led to reduced T<sub>FH</sub> cell responses. Mechanistically, miR-23~27~24 clusters coordinately control T<sub>FH</sub> cells through targeting a network of genes that are crucial for T<sub>FH</sub> cell biology. Among them, thymocyte selection-associated HMG-box protein (TOX) was identified as a central transcription regulator in T<sub>FH</sub> cell development. TOX is highly up-regulated in both mouse and human T<sub>FH</sub> cells in a BCL6-dependent manner. In turn, TOX promotes the expression of multiple molecules that play critical roles in T<sub>FH</sub> cell differentiation and function. Collectively, our results establish a key miRNA regulon that maintains optimal T<sub>FH</sub> cell responses for resultant humoral immunity.
Medical subject headings
- Cell Differentiation
- Immunity, Humoral
- T-Lymphocytes
- T-Lymphocytes, Helper-Inducer