%0 Journal Article
%T ABIN1 is a negative regulator of effector functions in cytotoxic T cells.
%A Janusova S
%A Paprckova D
%A Michalik J
%A Uleri V
%A Drobek A
%A Salyova E
%A Chorfi L
%A Neuwirth A
%A Andreyeva A
%A Prochazka J
%A Sedlacek R
%A Draber P
%A Stepanek O
%J EMBO Rep
%V 25
%N 8
%D 2024 Aug 14
%M 38877170
%F 9.071
%R 10.1038/s44319-024-00179-6
%X 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.