Year: 2016
Type: article
Abstract: Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LTαβ rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NFκB signalling via LTβR. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression.
Source: Nature Communications
DOI: 10.1038/ncomms12021
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: T-Cell Targeting for GVHD, In vivo Prevention of Murine GVHD, Mechanisms, Prevention and Treatment of Chronic Graft-vs.-Host Disease, Cytotoxic-T-Lymphocyte (CTL) Therapy of AML, Induction and Migration of Regulatory T Cells: Role of Lymphotoxin, T Cell Costimulatory Pathways: Functions and Interactions, Regulatory T Cells and Lymphatic Endothelial Cells: Regulatory Interactions for Migration and Suppression, Enhancing Treg Therapeutic Efficacy in GVHD, Training Grant in Cancer Biology, Off-the-Shelf Immune Effector Cells for Hematological Malignancies
OpenAlex ID: W2461482933