LINE1 modulate human T cell function by regulating protein synthesis during the life span

The molecular mechanisms responsible for the heightened reactivity of quiescent T cells in human early life remain largely elusive. Our previous research identified that quiescent adult naïve CD4 T cells express LINE1 (long interspersed nuclear elements 1) spliced in previously unknown isoforms, and...

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Published in:	Science advances Vol. 10; no. 41; p. eado2134
Main Authors:	Burattin, Filippo V, Vadalà, Rebecca, Panepuccia, Michele, Ranzani, Valeria, Crosti, Mariacristina, Colombo, Federico A, Ruberti, Cristina, Erba, Elisa, Prati, Daniele, Nittoli, Teresa, Montini, Giovanni, Ronchi, Andrea, Pugni, Lorenza, Mosca, Fabio, Ricciardi, Sara, Abrignani, Sergio, Pietrasanta, Carlo, Marasca, Federica, Bodega, Beatrice
Format:	Journal Article
Language:	English
Published:	United States American Association for the Advancement of Science 11-10-2024
Subjects:	Adult Aging - metabolism Biomedicine and Life Sciences CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Child Gene Expression Regulation Heterogeneous-Nuclear Ribonucleoproteins - genetics Heterogeneous-Nuclear Ribonucleoproteins - metabolism Humans Immunology Long Interspersed Nucleotide Elements Lymphocyte Activation Mechanistic Target of Rapamycin Complex 1 - metabolism Molecular Biology Polypyrimidine Tract-Binding Protein - genetics Polypyrimidine Tract-Binding Protein - metabolism Protein Biosynthesis Receptors, Antigen, T-Cell - metabolism SciAdv r-articles Signal Transduction T-Lymphocytes - immunology T-Lymphocytes - metabolism
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Summary:	The molecular mechanisms responsible for the heightened reactivity of quiescent T cells in human early life remain largely elusive. Our previous research identified that quiescent adult naïve CD4 T cells express LINE1 (long interspersed nuclear elements 1) spliced in previously unknown isoforms, and their down-regulation marks the transition to activation. Here, we unveil that neonatal naïve T cell quiescence is characterized by enhanced energy production and protein synthesis. This phenotype is associated with the absence of LINE1 expression attributed to tonic T cell receptor/mTOR complex 1 (mTORC1) signaling and (polypyrimidine tract-binding protein 1 (PTBP1)-mediated LINE1 splicing suppression. The absence of LINE1 expression primes these cells for rapid execution of the activation program by directly regulating protein synthesis. LINE1 expression progressively increases in childhood and adults, peaking in elderly individuals, and, by decreasing protein synthesis, contributes to immune senescence in aging. Our study proposes LINE1 as a critical player of human T cell function across the human life span.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	2375-2548 2375-2548
DOI:	10.1126/sciadv.ado2134