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

被引：69

作者：

Nores, Gabriela D. Garcia ^{[1
]}

Ly, Catherine L. ^{[1
]}

Cuzzone, Daniel A. ^{[1
]}

Kataru, Raghu P. ^{[1
]}

Hespe, Geoffrey E. ^{[1
]}

Torrisi, Jeremy S. ^{[1
]}

Huang, Jung Ju ^{[1
]}

Gardenier, Jason C. ^{[1
]}

Savetsky, Ira L. ^{[1
]}

Nitti, Matthew D. ^{[1
]}

Yu, Jessie Z. ^{[1
]}

Rehal, Sonia ^{[1
]}

Mehrara, Babak J. ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Surg, Div Plast & Reconstruct Surg, 1275 York Ave,Suite MRI 1006, New York, NY 10065 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

NITRIC-OXIDE; SECONDARY LYMPHEDEMA; MULTIPLE-SCLEROSIS; WOUND REPAIR; IN-VIVO; VEGF-C; LYMPHANGIOGENESIS; INFLAMMATION; MACROPHAGES; FIBROSIS;

D O I：

10.1038/s41467-018-04418-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 63 条

[1] Tissue-tropic effector T cells: generation and targeting opportunities [J].