Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27323847.
- Also identified by DOI 10.1038/ncomms12021 and PMC identifier 4919545.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Diabetes Mellitus, Experimental
- Graft Rejection
- Islets of Langerhans Transplantation
- Lymphotoxin alpha1, beta2 Heterotrimer
- Lymphotoxin beta Receptor
- T-Lymphocytes, Regulatory
- Transendothelial and Transepithelial Migration