N-Glycan Branching Regulates BTLA Opposite to PD-1 to Limit T Cell Hyperactivity Induced by Branching Deficiency.

Autor:	Mkhikian H; Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA., Zhou RW; Department of Neurology, University of California, Irvine, Irvine, CA., Saryan H; Department of Neurology, University of California, Irvine, Irvine, CA., Sánchez CD; Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA., Balakrishnan A; Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA., Dang J; Department of Neurology, University of California, Irvine, Irvine, CA., Mortales CL; Department of Neurology, University of California, Irvine, Irvine, CA., Demetriou M; Department of Neurology, University of California, Irvine, Irvine, CA.; Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Nov 01; Vol. 213 (9), pp. 1329-1337.
DOI:	10.4049/jimmunol.2300568
Abstrakt:	N-glycan branching is a potent and multifaceted negative regulator of proinflammatory T cell and B cell function. By promoting multivalent galectin-glycoprotein lattice formation at the cell surface, branching regulates clustering and/or endocytosis of the TCR complex (TCR+CD4/CD8), CD45, CD25, BCR, TLR2 and TLR4 to inhibit T cell and B cell activation/proliferation and proinflammatory TH1 and TH17 over TH2 and induced T regulatory cell responses. In addition, branching promotes cell surface retention of the growth inhibitory receptor CTLA-4. However, the role of N-glycan branching in regulating cell surface levels of other checkpoint receptors such as BTLA (B and T lymphocyte attenuator) and PD-1 (programmed cell death protein 1) is unknown. In this study, we report that whereas branching significantly enhances PD-1 cell surface expression by reducing loss from endocytosis, the opposite occurs with BTLA in both T cells and B cells. T cell hyperactivity induced by branching deficiency was opposed by BTLA ligation proportional to increased BTLA expression. Other members of the BTLA/HVEM (herpesvirus entry mediator) signaling axis in T cells, including HVEM, LIGHT, and CD160, are largely unaltered by branching. Thus, branching-mediated endocytosis of BTLA is opposite of branching-induced inhibition of PD-1 endocytosis. In this manner, branching deficiency-induced upregulation of BTLA appears to serve as a checkpoint to limit extreme T cell hyperactivity and proinflammatory outcomes in T cells with low branching. (Copyright © 2024 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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