T cells are pivotal in the adaptive immune defense, necessitating a delicate balance between robust response against infections and self-tolerance. Their activation involves intricate cross-talk among signaling pathways triggered by the T-cell antigen receptors (TCR) and co-stimulatory or inhibitory receptors. The molecular regulation of these complex signaling networks is still incompletely understood. Here, we identify the adaptor protein ABIN1 as a component of the signaling complexes of GITR and OX40 co-stimulation receptors. T cells lacking ABIN1 are hyper-responsive ex vivo, exhibit enhanced responses to cognate infections, and superior ability to induce experimental autoimmune diabetes in mice. ABIN1 negatively regulates p38 kinase activation and late NF-κB target genes. P38 is at least partially responsible for the upregulation of the key effector proteins IFNG and GZMB in ABIN1-deficient T cells after TCR stimulation. Our findings reveal the intricate role of ABIN1 in T-cell regulation.

• Keywords
• ABIN1, Antigen Receptor, Co-stimulation, T Cells, p38,
• MeSH
• Adaptor Proteins, Signal Transducing * metabolism   genetics   MeSH
• Lymphocyte Activation immunology   genetics   MeSH
• T-Lymphocytes, Cytotoxic * immunology   metabolism   MeSH
• Diabetes Mellitus, Type 1 immunology   genetics   metabolism   MeSH
• Glucocorticoid-Induced TNFR-Related Protein MeSH
• Interferon-gamma metabolism   MeSH
• Humans MeSH
• p38 Mitogen-Activated Protein Kinases metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Mice MeSH
• NF-kappa B metabolism   MeSH
• Receptors, Antigen, T-Cell metabolism   MeSH
• Receptors, OX40 metabolism   genetics   MeSH
• Signal Transduction * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Adaptor Proteins, Signal Transducing * MeSH
• Glucocorticoid-Induced TNFR-Related Protein MeSH
• Interferon-gamma MeSH
• p38 Mitogen-Activated Protein Kinases MeSH
• NF-kappa B MeSH
• Receptors, Antigen, T-Cell MeSH
• Receptors, OX40 MeSH
• Tnfrsf18 protein, mouse MeSH Browser