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J Invest Dermatol. 2018 Feb;138(2):325-335. doi: 10.1016/j.jid.2017.09.011. Epub 2017 Sep 20.

Regulatory T Cells Mediate Local Immunosuppression in Lymphedema.

Author information

1
The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
2
The Department of Medicine, Division of Cardiology, Stanford University Medical Center, Stanford, California, USA.
3
The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Electronic address: mehrarab@mskcc.org.

Abstract

Patients who suffer from lymphedema have impaired immunity and, as a result, are at an increased risk for infections. Furthermore, previous studies have shown that lymphadenectomy impairs acquisition of adaptive immune responses and antibody production in response to foreign antigens. Although it is clear that antigen presentation in lymph nodes plays a key role in adaptive immunity, the cellular mechanisms that regulate impaired immune responses in patients with lymphedema or following lymphatic injury remain unknown. We have previously found that axillary lymph node dissection, both clinically and in a mouse model, results in a marked increase in the number of regulatory T cells in the ipsilateral limb. In this study, we focus on the role of regulatory T cells in immunosuppression and show that regulatory T-cell proliferation in tissues distal to site of lymphatic injury contributes to impaired innate and adaptive immune responses. More importantly, using Foxp3-DTR transgenic mice, we show that depletion of regulatory T cells in the setting of lymphatic injury restores these critical immune-mediated responses. These findings provide additional evidence that immune responses following lymphatic injury play a key role in mediating the pathology of lymphedema.

PMID:
28942366
PMCID:
PMC5794510
DOI:
10.1016/j.jid.2017.09.011
[Indexed for MEDLINE]
Free PMC Article

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