Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin.

Abstract

Thymic Stromal Lymphopoietin (TSLP), a cytokine implicated in induction of T helper 2 (Th2)-mediated allergic inflammation, has recently been shown to stimulate solid tumor growth and metastasis. Conversely, studying mice with clonal loss of Notch signaling in their skin revealed that high levels of TSLP released by barrier-defective skin caused a severe inflammation, resulting in gradual elimination of Notch-deficient epidermal clones and resistance to skin tumorigenesis. We found CD4(+) T cells to be both required and sufficient to mediate these effects of TSLP. Importantly, TSLP overexpression in wild-type skin also caused resistance to tumorigenesis, confirming that TSLP functions as a tumor suppressor in the skin.

• Authors: Shadmehr Demehri, Ahu Turkoz, Sindhu Manivasagam, Laura J Yockey, Mustafa Turkoz, Raphael Kopan
• Journal: Cancer cell (Cancer Cell) Vol. 22 Issue 4 Pg. 494-505 (Oct 16 2012) ISSN: 1878-3686 [Electronic] United States
• PMID: 23079659 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Receptors, Notch
• Tumor Suppressor Proteins
• Thymic Stromal Lymphopoietin
• TSLP protein, mouse

Topics

• Adaptive Immunity
• Animals
• CD4-Positive T-Lymphocytes (physiology)
• Cytokines (analysis, physiology)
• Dermatitis (complications)
• Genes, ras
• Mice
• Mice, Inbred C57BL
• Receptors, Notch (physiology)
• Signal Transduction
• Skin (immunology)
• Skin Neoplasms (prevention & control)
• Tumor Suppressor Proteins (physiology)
• Thymic Stromal Lymphopoietin