CD4+ T cells are activated in regional lymph nodes and migrate to skin to initiate lymphedema

Nature Communications
Gabriela D García NoresBabak J Mehrara

Abstract

T cell-mediated responses have been implicated in the development of fibrosis, impaired lymphangiogenesis, and lymphatic dysfunction in secondary lymphedema. Here we show that CD4+ T cells are necessary for lymphedema pathogenesis by utilizing adoptive transfer techniques in CD4 knockout mice that have undergone tail skin and lymphatic excision or popliteal lymph node dissection. We also demonstrate that T cell activation following lymphatic injury occurs in regional skin-draining lymph nodes after interaction with antigen-presenting cells such as dendritic cells. CD4+ T cell activation is associated with differentiation into a mixed T helper type 1 and 2 phenotype, as well as upregulation of adhesion molecules and chemokines that promote migration to the skin. Most importantly, we find that blocking T cell release from lymph nodes using a sphingosine-1-phosphate receptor modulator prevents lymphedema, suggesting that this approach may have clinical utility.

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Feb 12, 2019·Annual Review of Physiology·Massimiliano Mazzone, Gabriele Bergers
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Methods Mentioned

BETA
biopsy
dissection
fluorescence-activated
fluorescence-activated cell sorting
transgenic
mechanical dissociation
flow cytometry
PCR

Software Mentioned

Metamorph Offline
GraphPad Prism
ASIPro
Fiji
Pannoramic Viewer
FlowJo
ImageJ

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