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N6-Methyladenosine Directly Regulates CD40L Expression in CD4+ T Lymphocytes.
van Vroonhoven, Ellen C N; Picavet, Lucas W; Scholman, Rianne C; van den Dungen, Noortje A M; Mokry, Michal; Evers, Anouk; Lebbink, Robert J; Calis, Jorg J A; Vastert, Sebastiaan J; van Loosdregt, Jorg.
Afiliação
  • van Vroonhoven ECN; Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Picavet LW; Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Scholman RC; Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • van den Dungen NAM; Department of Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Mokry M; Department of Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Evers A; Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Lebbink RJ; Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Calis JJA; Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Vastert SJ; Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • van Loosdregt J; Department of Pediatric Rheumatology and Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Biology (Basel) ; 12(7)2023 Jul 14.
Article em En | MEDLINE | ID: mdl-37508433
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Biology (Basel) Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Biology (Basel) Ano de publicação: 2023 Tipo de documento: Article