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ABIN1 is a negative regulator of effector functions in cytotoxic T cells

ABSTRACT: 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.

SUBMITTER: Sarka Janusova

PROVIDER: S-SCDT-10_1038-S44319-024-00179-6 | biostudies-other |

REPOSITORIES: biostudies-other

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ABIN1 is a negative regulator of effector functions in cytotoxic T cells.

Project description: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.

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ABIN1 is a negative regulator of effector functions in cytotoxic T cells

Project description:The main objective of the data analysis presented here is the investigation of the role of ABIN1 in antigenic responses of primary T cells. For this purpose, T cells from ABIN1-deficient mouse strain (GTKO) and WT mice were analyzed under different activation conditions. The effect of P38 MAPK inhibitor SB203580 (p38 inhibitor/p38i) was also analyzed. The results suggest that ABIN1 is a negative regulator of TCR-mediated activation and expression of the key effector molecules in primary CD8+ T cells, at least partly via the inhibition of the p38 pathway.

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