title: Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma.
abstract: Thymic stromal lymphopoietin (TSLP) activates dendritic cells to induce Th2-mediated inflammation. Periostin, an extracellular matrix protein produced by fibroblasts, induces chronic inflammation by stimulating TSLP production. Recently, a reinforcing cycle linking Th2-type immune responses with periostin-induced keratinocyte activation has been proposed in atopic dermatitis pathogenesis. In this study, we investigated the role of TSLP and periostin in the development of cutaneous T-cell lymphoma (CTCL), where Th2 cytokines and chemokines are also dominant. TSLP and periostin mRNA expression levels were elevated in CTCL lesional skin, both of which correlated with IL4 expression levels. In vitro and ex vivo, IL4 or IL13 stimulated periostin expression by dermal fibroblasts, and fibroblasts from CTCL lesional skin expressed higher levels of periostin than those from control skin. Serum periostin levels of CTCL patients were also significantly higher than those of healthy individuals. Hut78 and MJ, CTCL cell lines, and peripheral blood mononuclear cells from leukemic CTCL patients expressed the TSLP receptor. TSLP induced production of IL4 and IL13 by Hut78 and MJ cells through the activation of STAT5. Moreover, TSLP induced proliferation of CTCL cells both in vitro and in vivo These data suggest that periostin-mediated TSLP production by keratinocytes directly stimulates CTCL tumor cell growth in addition to inducing a Th2-dominant tumor environment in CTCL. Cancer Res; 76(21); 6241-52. ©2016 AACR.
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan. sugayam-der@h.u-tokyo.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugaya
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hiraku
authors.initials: H
authors.lastname: Suga
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Oka
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kawaguchi
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyagaki
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015815:Cell Adhesion Molecules / Q000097:blood / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016410:Lymphoma, T-Cell, Cutaneous / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018121:Receptors, Cytokine / Q000032:analysis; D050799:STAT5 Transcription Factor / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: C498762:CRLF2 protein, human; D015815:Cell Adhesion Molecules; D016207:Cytokines; D018793:Interleukin-13; C512835:POSTN protein, human; D018121:Receptors, Cytokine; D050799:STAT5 Transcription Factor; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin