CoChat
Sign Up
Cited by 241Lymphatic System and DiseasesLymphatic Disorders and TreatmentsParasitic Diseases Research and Treatment

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema

Open access
Avraham, Tomer, Zampell, Jamie C., Yan, Alan, Elhadad, Sonia, Weitman, Evan S., Rockson, Stanley G., Bromberg, Jacqueline, Mehrara, Babak J.·2013·The FASEB Journal
DOI 10.1096/fj.12-222695PMC PMC3574290
Open this paper in CoChat — free account

Abstract

Lymphedema is a dreaded complication of cancer treatment. However, despite the fact that >5 million Americans are affected by this disorder, the development of effective treatments is limited by the fact that the pathology of lymphedema remains unknown. The purpose of these studies was to determine the role of inflammatory responses in lymphedema pathology. Using mouse models of lymphedema, as well as clinical lymphedema specimens, we show that lymphatic stasis results in a CD4 T-cell inflammation and T-helper 2 (Th2) differentiation. Using mice deficient in T cells or CD4 cells, we show that this inflammatory response is necessary for the pathological changes of lymphedema, including fibrosis, adipose deposition, and lymphatic dysfunction. Further, we show that inhibition of Th2 differentiation using interleukin-4 (IL-4) or IL-13 blockade prevents initiation and progression of lymphedema by decreasing tissue fibrosis and significantly improving lymphatic function, independent of lymphangiogenic growth factors. We show that CD4 inflammation is a critical regulator of tissue fibrosis and lymphatic dysfunction in lymphedema and that inhibition of Th2 differentiation markedly improves lymphatic function independent of lymphangiogenic cytokine expression. Notably, preventing and/or reversing the development of pathological tissue changes that occur in lymphedema may be a viable treatment strategy for this disorder.

Overview

Integrity signals

Registry

Crossref · 10.1096/fj.12-222695

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. 10.1002/(SICI)1097-0142(19981215)83:12B <2776::AID-CNCR25>3.0.CO;2-V · DOI

Cited by

Sorted by citations

See all 241

Related

See all

Metadata

Authors
Avraham, T., Zampell, J. C., Yan, A., Elhadad, S., Weitman, E. S., Rockson, S. G., Bromberg, J., & Mehrara, B. J.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Division of Plastic and Reconstructive Surgery Department of Surgery New York New York USA
  • Stanford Medicine (US)
ORCID
Venue
The FASEB Journal
Publisher
Wiley
Published
2012-11-27
Volume
27
Issue
3
Pages
1114-1126
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
DOI
10.1096/fj.12-222695
PMC
PMC3574290
OpenAlex
W2102471792
Cited by
241
References
42
Citations by year
2026: 22 · 2025: 21 · 2024: 19 · 2023: 26 · 2022: 24 · 2021: 24 · 2020: 16 · 2019: 21 · 2018: 12 · 2017: 16 · 2016: 10 · 2015: 12 · 2014: 12 · 2013: 4
FWCI
4.43
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The FASEB Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Defense (BC103691)
  • National Heart, Lung, and Blood Institute
  • National Institutes of Health (R01HL111130)
  • Center for Scientific Review (P30 CA08748)
Topics
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
  • Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
Keywords
lymphedema, Th2 differentiation, fibrosis, lymphatic dysfunction, lymphatic stasis, IL-4, IL-13, lymphangiogenesis, cancer treatment complications, lymphedema treatment
MeSH terms
Animals, Cell Differentiation, Disease Models, Animal, Fibrosis, Inflammation, Lymphedema, Mice, Nude, Interleukin-4, Mice, Knockout, Th2 Cells, Interleukin-13, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review