Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4<sup>+</sup>, CD8<sup>+</sup>, and Foxp3<sup>+</sup> Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis
Chemokines and cytokines in the tumor microenvironment influence immune cell infiltration and activation. To elucidate their role in immune cell recruitment during oral cancer development, we generated a mouse tongue cancer model using the carcinogen 4-nitroquinoline 1-oxide (4NQO) and investigated...
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MDPI AG
2021-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/8/1835 |
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| author | Hana Yamaguchi Miki Hiroi Kazumasa Mori Ryosuke Ushio Ari Matsumoto Nobuharu Yamamoto Jun Shimada Yoshihiro Ohmori |
| author_facet | Hana Yamaguchi Miki Hiroi Kazumasa Mori Ryosuke Ushio Ari Matsumoto Nobuharu Yamamoto Jun Shimada Yoshihiro Ohmori |
| author_sort | Hana Yamaguchi |
| collection | DOAJ |
| description | Chemokines and cytokines in the tumor microenvironment influence immune cell infiltration and activation. To elucidate their role in immune cell recruitment during oral cancer development, we generated a mouse tongue cancer model using the carcinogen 4-nitroquinoline 1-oxide (4NQO) and investigated the carcinogenetic process and chemokine/cytokine gene expression kinetics in the mouse tongue. C57/BL6 mice were administered 4NQO in drinking water, after which tongues were dissected at 16 and 28 weeks and subjected to analysis using the RT<sup>2</sup> Profiler PCR Array, qRT-PCR, and pathologic and immunohistochemical analyses. We found that Th1-associated chemokine/cytokine (<i>Cxcl9</i>, <i>Cxcl10</i>, <i>Ccl5</i>, and <i>Ifng</i>) and Treg-associated chemokine/cytokine (<i>Ccl17</i>, <i>Ccl22</i>, and <i>Il10</i>) mRNA levels were simultaneously increased in premalignant lesions of 4NQO-treated mice at 16 weeks. Additionally, although levels of <i>Gata3</i>, a Th2 marker, were not upregulated, those of <i>Cxcr3</i>, <i>Ccr4</i>, and <i>Foxp3</i> were upregulated in the tongue tissue. Furthermore, immunohistochemical analysis confirmed the infiltration of CD4<sup>+</sup>, CD8<sup>+</sup>, and Foxp3<sup>+</sup> cells in the tongue tissue of 4NQO-treated mice, as well as significant correlations between Th1- or Treg-associated chemokine/cytokine mRNA expression and T cell infiltration. These results indicate that CD4<sup>+</sup>, CD8<sup>+</sup>, and Foxp3<sup>+</sup> cells were simultaneously recruited through the expression of Th1- and Treg-associated chemokines in premalignant lesions of 4NQO-induced mouse tongue tissue. |
| first_indexed | 2024-03-10T12:24:32Z |
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| id | doaj.art-dac27e23b7c0436e80e58d772aae4e5a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T12:24:32Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-dac27e23b7c0436e80e58d772aae4e5a2023-11-21T15:12:22ZengMDPI AGCancers2072-66942021-04-01138183510.3390/cancers13081835Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4<sup>+</sup>, CD8<sup>+</sup>, and Foxp3<sup>+</sup> Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue TumorigenesisHana Yamaguchi0Miki Hiroi1Kazumasa Mori2Ryosuke Ushio3Ari Matsumoto4Nobuharu Yamamoto5Jun Shimada6Yoshihiro Ohmori7Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, JapanDivision of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, JapanFirst Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, JapanDivision of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, JapanDivision of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, JapanFirst Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, JapanFirst Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, JapanDivision of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, JapanChemokines and cytokines in the tumor microenvironment influence immune cell infiltration and activation. To elucidate their role in immune cell recruitment during oral cancer development, we generated a mouse tongue cancer model using the carcinogen 4-nitroquinoline 1-oxide (4NQO) and investigated the carcinogenetic process and chemokine/cytokine gene expression kinetics in the mouse tongue. C57/BL6 mice were administered 4NQO in drinking water, after which tongues were dissected at 16 and 28 weeks and subjected to analysis using the RT<sup>2</sup> Profiler PCR Array, qRT-PCR, and pathologic and immunohistochemical analyses. We found that Th1-associated chemokine/cytokine (<i>Cxcl9</i>, <i>Cxcl10</i>, <i>Ccl5</i>, and <i>Ifng</i>) and Treg-associated chemokine/cytokine (<i>Ccl17</i>, <i>Ccl22</i>, and <i>Il10</i>) mRNA levels were simultaneously increased in premalignant lesions of 4NQO-treated mice at 16 weeks. Additionally, although levels of <i>Gata3</i>, a Th2 marker, were not upregulated, those of <i>Cxcr3</i>, <i>Ccr4</i>, and <i>Foxp3</i> were upregulated in the tongue tissue. Furthermore, immunohistochemical analysis confirmed the infiltration of CD4<sup>+</sup>, CD8<sup>+</sup>, and Foxp3<sup>+</sup> cells in the tongue tissue of 4NQO-treated mice, as well as significant correlations between Th1- or Treg-associated chemokine/cytokine mRNA expression and T cell infiltration. These results indicate that CD4<sup>+</sup>, CD8<sup>+</sup>, and Foxp3<sup>+</sup> cells were simultaneously recruited through the expression of Th1- and Treg-associated chemokines in premalignant lesions of 4NQO-induced mouse tongue tissue.https://www.mdpi.com/2072-6694/13/8/1835chemokineTh1Th2TregFoxp3gene expression |
| spellingShingle | Hana Yamaguchi Miki Hiroi Kazumasa Mori Ryosuke Ushio Ari Matsumoto Nobuharu Yamamoto Jun Shimada Yoshihiro Ohmori Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4<sup>+</sup>, CD8<sup>+</sup>, and Foxp3<sup>+</sup> Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis Cancers chemokine Th1 Th2 Treg Foxp3 gene expression |
| title | Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4<sup>+</sup>, CD8<sup>+</sup>, and Foxp3<sup>+</sup> Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis |
| title_full | Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4<sup>+</sup>, CD8<sup>+</sup>, and Foxp3<sup>+</sup> Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis |
| title_fullStr | Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4<sup>+</sup>, CD8<sup>+</sup>, and Foxp3<sup>+</sup> Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis |
| title_full_unstemmed | Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4<sup>+</sup>, CD8<sup>+</sup>, and Foxp3<sup>+</sup> Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis |
| title_short | Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4<sup>+</sup>, CD8<sup>+</sup>, and Foxp3<sup>+</sup> Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis |
| title_sort | simultaneous expression of th1 and treg associated chemokine genes and cd4 sup sup cd8 sup sup and foxp3 sup sup cells in the premalignant lesions of 4nqo induced mouse tongue tumorigenesis |
| topic | chemokine Th1 Th2 Treg Foxp3 gene expression |
| url | https://www.mdpi.com/2072-6694/13/8/1835 |
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