author_facet Takahashi, Naomi
Sugaya, Makoto
Suga, Hiraku
Oka, Tomonori
Kawaguchi, Makiko
Miyagaki, Tomomitsu
Fujita, Hideki
Sato, Shinichi
Takahashi, Naomi
Sugaya, Makoto
Suga, Hiraku
Oka, Tomonori
Kawaguchi, Makiko
Miyagaki, Tomomitsu
Fujita, Hideki
Sato, Shinichi
author Takahashi, Naomi
Sugaya, Makoto
Suga, Hiraku
Oka, Tomonori
Kawaguchi, Makiko
Miyagaki, Tomomitsu
Fujita, Hideki
Sato, Shinichi
spellingShingle Takahashi, Naomi
Sugaya, Makoto
Suga, Hiraku
Oka, Tomonori
Kawaguchi, Makiko
Miyagaki, Tomomitsu
Fujita, Hideki
Sato, Shinichi
Cancer Research
Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
Cancer Research
Oncology
author_sort takahashi, naomi
spelling Takahashi, Naomi Sugaya, Makoto Suga, Hiraku Oka, Tomonori Kawaguchi, Makiko Miyagaki, Tomomitsu Fujita, Hideki Sato, Shinichi 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-16-0992 <jats:title>Abstract</jats:title><jats:p>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.</jats:p> Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma Cancer Research
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title Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
title_unstemmed Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
title_full Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
title_fullStr Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
title_full_unstemmed Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
title_short Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
title_sort thymic stromal chemokine tslp acts through th2 cytokine production to induce cutaneous t-cell lymphoma
topic Cancer Research
Oncology
url http://dx.doi.org/10.1158/0008-5472.can-16-0992
publishDate 2016
physical 6241-6252
description <jats:title>Abstract</jats:title><jats:p>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.</jats:p>
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author Takahashi, Naomi, Sugaya, Makoto, Suga, Hiraku, Oka, Tomonori, Kawaguchi, Makiko, Miyagaki, Tomomitsu, Fujita, Hideki, Sato, Shinichi
author_facet Takahashi, Naomi, Sugaya, Makoto, Suga, Hiraku, Oka, Tomonori, Kawaguchi, Makiko, Miyagaki, Tomomitsu, Fujita, Hideki, Sato, Shinichi, Takahashi, Naomi, Sugaya, Makoto, Suga, Hiraku, Oka, Tomonori, Kawaguchi, Makiko, Miyagaki, Tomomitsu, Fujita, Hideki, Sato, Shinichi
author_sort takahashi, naomi
container_issue 21
container_start_page 6241
container_title Cancer Research
container_volume 76
description <jats:title>Abstract</jats:title><jats:p>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.</jats:p>
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imprint_str_mv American Association for Cancer Research (AACR), 2016
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spelling Takahashi, Naomi Sugaya, Makoto Suga, Hiraku Oka, Tomonori Kawaguchi, Makiko Miyagaki, Tomomitsu Fujita, Hideki Sato, Shinichi 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-16-0992 <jats:title>Abstract</jats:title><jats:p>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.</jats:p> Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma Cancer Research
spellingShingle Takahashi, Naomi, Sugaya, Makoto, Suga, Hiraku, Oka, Tomonori, Kawaguchi, Makiko, Miyagaki, Tomomitsu, Fujita, Hideki, Sato, Shinichi, Cancer Research, Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma, Cancer Research, Oncology
title Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
title_full Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
title_fullStr Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
title_full_unstemmed Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
title_short Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
title_sort thymic stromal chemokine tslp acts through th2 cytokine production to induce cutaneous t-cell lymphoma
title_unstemmed Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
topic Cancer Research, Oncology
url http://dx.doi.org/10.1158/0008-5472.can-16-0992