N6-Methyladenosine Directly Regulates CD40L Expression in CD4+ T Lymphocytes.
Biology (Basel)
; 12(7)2023 Jul 14.
Article
em En
| MEDLINE
| ID: mdl-37508433
ABSTRACT
T cell activation is a highly regulated process, modulated via the expression of various immune regulatory proteins including cytokines, surface receptors and co-stimulatory proteins. N6-methyladenosine (m6A) is an RNA modification that can directly regulate RNA expression levels and it is associated with various biological processes. However, the function of m6A in T cell activation remains incompletely understood. We identify m6A as a novel regulator of the expression of the CD40 ligand (CD40L) in human CD4+ lymphocytes. Manipulation of the m6A 'eraser' fat mass and obesity-associated protein (FTO) and m6A 'writer' protein methyltransferase-like 3 (METTL3) directly affects the expression of CD40L. The m6A 'reader' protein YT521-B homology domain family-2 (YTHDF2) is hypothesized to be able to recognize and bind m6A specific sequences on the CD40L mRNA and promotes its degradation. This study demonstrates that CD40L expression in human primary CD4+ T lymphocytes is regulated via m6A modifications, elucidating a new regulatory mechanism in CD4+ T cell activation that could possibly be leveraged in the future to modulate T cell responses in patients with immune-related diseases.
Texto completo:
1
Base de dados:
MEDLINE
Idioma:
En
Revista:
Biology (Basel)
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Holanda