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Analysis of GITR and OX40 signaling complexes

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. We identified an adaptor protein, ABIN1 as a component of the signaling complexes of GITR and OX40 co-stimulation receptors. T cells lacking ABIN1 exhibit hyper-responsiveness to TCR activation ex vivo, enhanced responses to cognate infections, and superior ability to induce experimental autoimmune diabetes in mice. We observed that ABIN1 negatively regulates NFκB and p38 pathways. The latter was at least partially responsible for the upregulation of 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 and its potential as a target for therapeutic fine-tuning T-cell responses.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): T Cell, Cell Culture

SUBMITTER: Peter Draber

LAB HEAD: Peter Draber

PROVIDER: PXD046422 | Pride | 2024-04-25

REPOSITORIES: Pride

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