Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin.
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.
Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St. Louis, MO 63110-1095, USA. demehris@wustl.edu
Shadmehr
S
Demehri
Ahu
A
Turkoz
Sindhu
S
Manivasagam
Laura J
LJ
Yockey
Mustafa
M
Turkoz
Raphael
R
Kopan
D056704:Adaptive Immunity; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016207:Cytokines / Q000032:analysis / Q000502:physiology*; D003872:Dermatitis / Q000150:complications; D011905:Genes, ras; D051379:Mice; D008810:Mice, Inbred C57BL; D051880:Receptors, Notch / Q000502:physiology; D015398:Signal Transduction; D012867:Skin / Q000276:immunology*; D012878:Skin Neoplasms / Q000517:prevention & control*; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D051880:Receptors, Notch; D025521:Tumor Suppressor Proteins; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse