The english version of the website is under development. Wherever text appears in Greek, it means it has not been translated yet.

Δημοσίευση

Regulatory T cell transfer ameliorates lymphedema and promotes lymphatic vessel function.

TitleRegulatory T cell transfer ameliorates lymphedema and promotes lymphatic vessel function.
Publication TypeJournal Article
Year of Publication2016
AuthorsGousopoulos, E., Proulx S. T., Bachmann S. B., Scholl J., Dionyssiou D., Demiri E., Halin C., Dieterich L. C., & Detmar M.
JournalJCI Insight
Volume1
Issue16
Paginatione89081
Date Published2016 10 06
ISSN2379-3708
Abstract

Secondary lymphedema is a common postcancer treatment complication, but the underlying pathological processes are poorly understood and no curative treatment exists. To investigate lymphedema pathomechanisms, a top-down approach was applied, using genomic data and validating the role of a single target. RNA sequencing of lymphedematous mouse skin indicated upregulation of many T cell-related networks, and indeed depletion of CD4 cells attenuated lymphedema. The significant upregulation of Foxp3, a transcription factor specifically expressed by regulatory T cells (Tregs), along with other Treg-related genes, implied a potential role of Tregs in lymphedema. Indeed, increased infiltration of Tregs was identified in mouse lymphedematous skin and in human lymphedema specimens. To investigate the role of Tregs during disease progression, loss-of-function and gain-of-function studies were performed. Depletion of Tregs in transgenic mice with Tregs expressing the primate diphtheria toxin receptor and green fluorescent protein (-DTR-GFP) mice led to exacerbated edema, concomitant with increased infiltration of immune cells and a mixed T1/T2 cytokine profile. Conversely, expansion of Tregs using IL-2/anti-IL-2 mAb complexes significantly reduced lymphedema development. Therapeutic application of adoptively transferred Tregs upon lymphedema establishment reversed all of the major hallmarks of lymphedema, including edema, inflammation, and fibrosis, and also promoted lymphatic drainage function. Collectively, our results reveal that Treg application constitutes a potential new curative treatment modality for lymphedema.

DOI10.1172/jci.insight.89081
Alternate JournalJCI Insight
PubMed ID27734032
PubMed Central IDPMC5054740

Contact

Secretariat of the School of Medicine
 

Connect

School of Medicine's presence in social networks
Follow Us or Connect with us.