ISG20L2: an RNA nuclease regulating T cell activation

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Authors

RODRIGUEZ-GALAN Ana DOSIL Sara G VLČKOVÁ Anna FERNANDEZ-MESSINA Lola FEKETOVÁ Zuzana POKORNÁ Julie FERNANDEZ-DELGADO Irene CAMAFEITA Emilio GOMEZ Manuel Jose RAMIREZ-HUESCA Marta GUTIERREZ-VAZQUEZ Cristina SANCHEZ-CABO Fatima VAZQUEZ Jesus VAŇÁČOVÁ Štěpánka SANCHEZ-MADRID Francisco

Year of publication 2023
Type Article in Periodical
Magazine / Source Cellular and molecular life sciences
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://link.springer.com/article/10.1007/s00018-023-04925-2
Doi http://dx.doi.org/10.1007/s00018-023-04925-2
Keywords Exonuclease; T cell; Immunoregulatory
Description ISG20L2, a 3' to 5' exoribonuclease previously associated with ribosome biogenesis, is identified here in activated T cells as an enzyme with a preferential affinity for uridylated miRNA substrates. This enzyme is upregulated in T lymphocytes upon TCR and IFN type I stimulation and appears to be involved in regulating T cell function. ISG20L2 silencing leads to an increased basal expression of CD69 and induces greater IL2 secretion. However, ISG20L2 absence impairs CD25 upregula-tion, CD3 synaptic accumulation and MTOC translocation towards the antigen-presenting cell during immune synapsis. Remarkably, ISG20L2 controls the expression of immunoregulatory molecules, such as AHR, NKG2D, CTLA-4, CD137, TIM-3, PD-L1 or PD-1, which show increased levels in ISG20L2 knockout T cells. The dysregulation observed in these key molecules for T cell responses support a role for this exonuclease as a novel RNA-based regulator of T cell function.
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