Transcriptomics

Dataset Information

0

Mettl14-dependent m6A modification controls iNKT cells development and function by regulating p53-dependent apoptosis pathway and TCR signaling


ABSTRACT: N6-methyladenosine (m6A) is the most common modification to mRNA in mammalian cells linked to development and disease. m6A controls CD4+ T cell homeostasis by targeting the IL-7/STAT5/SOCS family pathway and sustains Treg suppressive function. However, the role of m6A modification in non-conventional T cell development and function remains unknown. Here we showed that m6A modification was indispensable for NKT cell homeostasis using mice with T cell-specific deletion of RNA methylation writer METTL14 (T-Mettl14-/-). Loss of METTL14-dependent m6A modification led to the upregulation of p53-mediated apoptosis in double-positive (DP) thymocytes. The decreased lifespan of DP thymocytes reduced the efficiency of distal Va-Ja rearrangement, including the invariant Va14-Ja18 TCR, and therefore led to a profound decrease in the iNKT cell population. The residual iNKT cells in T-Mettl14-/- mice exhibited increased apoptosis and impaired maturation. In addition, loss of METTL14 upregulated Cish expression, which contributed to decreased proliferative response to IL-2 and IL-15 and impaired cytokine production upon TCR stimulation in METTL14-deficient iNKT cells. Furthermore, knocking down METTL14 in mature iNKT cells diminished their cytokine production, correlated with increased Cish expression and decreased TCR signaling. Collectively, our data reveals a critical role for METTL14- dependent-m6A modification in iNKT cell development and function, highlighting the need to take this effect into consideration for targeting m6A pathway in therapeutic settings.

ORGANISM(S): Mus musculus

PROVIDER: GSE189339 | GEO | 2022/03/01

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2023-12-31 | GSE210325 | GEO
2021-09-02 | GSE182995 | GEO
2022-08-11 | GSE156013 | GEO
2023-12-31 | GSE210324 | GEO
2015-02-27 | E-GEOD-56010 | biostudies-arrayexpress
2022-08-10 | GSE130184 | GEO
2021-05-21 | GSE149176 | GEO
2021-05-21 | GSE149174 | GEO
2019-01-20 | GSE109530 | GEO
2019-01-20 | GSE109529 | GEO