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

TL;DR

ABIN1 limits the activity of cytotoxic T cells by controlling key signaling pathways, which helps maintain immune balance and prevent autoimmunity.

Contribution

ABIN1 is newly identified as a negative regulator of T-cell effector functions through p38 and NF-κB signaling.

Findings

ABIN1-deficient T cells show enhanced responses to infections and autoimmunity in mice.

ABIN1 restricts p38 activation and late NF-κB target genes in T cells.

ABIN1 contributes to peripheral tolerance by limiting effector cell formation.

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.

The adaptor protein ABIN1 is a negative regulator of antigenic and co-stimulation signaling in T cells. ABIN1 limits cytotoxic T-cell effector functions by restricting p38 activation.

ABIN1 and A20 are recruited to GITR and OX40 signaling complexes.ABIN1 negatively regulates p38 activation and the induction of late NF-κB response genes upon antigenic signaling in T cells.ABIN1-deficient cytotoxic T cells upregulate effector genes upon activation in a p38-dependent manner.ABIN1 limits the formation of effector cells upon antigenic activation in vivo and contributes to peripheral tolerance.

ABIN1 and A20 are recruited to GITR and OX40 signaling complexes.

ABIN1 negatively regulates p38 activation and the induction of late NF-κB response genes upon antigenic signaling in T cells.

ABIN1-deficient cytotoxic T cells upregulate effector genes upon activation in a p38-dependent manner.

ABIN1 limits the formation of effector cells upon antigenic activation in vivo and contributes to peripheral tolerance.

The adaptor protein ABIN1 is a negative regulator of antigenic and co-stimulation signaling in T cells. ABIN1 limits cytotoxic T-cell effector functions by restricting p38 activation.

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