IL-32 induces indoleamine 2,3-dioxygenase+CD1c+ dendritic cells and indoleamine 2,3-dioxygenase+CD163+ macrophages: Relevance to mycosis fungoides progression
Mycosis fungoides (MF) progresses from patch to tumor stage by expansion of malignant T-cells that fail to be controlled by protective immune mechanisms. In this study, we focused on IL-32, a cytokine, highly expressed in MF lesions. Depending on the other cytokines (IL-4, GM-CSF) present during in...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-02-01
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| Series: | OncoImmunology |
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| Online Access: | http://dx.doi.org/10.1080/2162402X.2016.1181237 |
| _version_ | 1818281826148417536 |
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| author | Hanako Ohmatsu Daniel Humme Juana Gonzalez Nicholas Gulati Markus Möbs Wolfram Sterry James G. Krueger |
| author_facet | Hanako Ohmatsu Daniel Humme Juana Gonzalez Nicholas Gulati Markus Möbs Wolfram Sterry James G. Krueger |
| author_sort | Hanako Ohmatsu |
| collection | DOAJ |
| description | Mycosis fungoides (MF) progresses from patch to tumor stage by expansion of malignant T-cells that fail to be controlled by protective immune mechanisms. In this study, we focused on IL-32, a cytokine, highly expressed in MF lesions. Depending on the other cytokines (IL-4, GM-CSF) present during in vitro culture of healthy volunteers' monocytes, IL-32 increased the maturation of CD11c+ myeloid dendritic cells (mDC) and/or CD163+ macrophages, but IL-32 alone showed a clear ability to promote dendritic cell (DC) differentiation from monocytes. DCs matured by IL-32 had the phenotype of skin-resident DCs (CD1c+), but more importantly, also had high expression of indoleamine 2,3-dioxygenase. The presence of DCs with these markers was demonstrated in MF skin lesions. At a molecular level, indoleamine 2,3-dioxygenase messenger RNA (mRNA) levels in MF lesions were higher than those in healthy volunteers, and there was a high correlation between indoleamine 2,3-dioxygenase and IL-32 expression. In contrast, Foxp3 mRNA levels decreased from patch to tumor stage. Increasing expression of IL-10 across MF lesions was highly correlated with IL-32 and indoleamine 2,3-dioxygenase, but not with Foxp3 expression. Thus, IL-32 could contribute to progressive immune dysregulation in MF by directly fostering development of immunosuppressive mDC or macrophages, possibly in association with IL-10. |
| first_indexed | 2024-12-13T00:11:17Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-13T00:11:17Z |
| publishDate | 2017-02-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-442960cd813940968856f52f2e2aea342022-12-22T00:05:57ZengTaylor & Francis GroupOncoImmunology2162-402X2017-02-016210.1080/2162402X.2016.11812371181237IL-32 induces indoleamine 2,3-dioxygenase+CD1c+ dendritic cells and indoleamine 2,3-dioxygenase+CD163+ macrophages: Relevance to mycosis fungoides progressionHanako Ohmatsu0Daniel Humme1Juana Gonzalez2Nicholas Gulati3Markus Möbs4Wolfram Sterry5James G. Krueger6Laboratory for Investigative Dermatology, The Rockefeller UniversitySkin Cancer Center Charité, Charité- Universitätsmedizin BerlinRockefeller University Center for Clinical and Translational ScienceLaboratory for Investigative Dermatology, The Rockefeller UniversitySkin Cancer Center Charité, Charité- Universitätsmedizin BerlinSkin Cancer Center Charité, Charité- Universitätsmedizin BerlinLaboratory for Investigative Dermatology, The Rockefeller UniversityMycosis fungoides (MF) progresses from patch to tumor stage by expansion of malignant T-cells that fail to be controlled by protective immune mechanisms. In this study, we focused on IL-32, a cytokine, highly expressed in MF lesions. Depending on the other cytokines (IL-4, GM-CSF) present during in vitro culture of healthy volunteers' monocytes, IL-32 increased the maturation of CD11c+ myeloid dendritic cells (mDC) and/or CD163+ macrophages, but IL-32 alone showed a clear ability to promote dendritic cell (DC) differentiation from monocytes. DCs matured by IL-32 had the phenotype of skin-resident DCs (CD1c+), but more importantly, also had high expression of indoleamine 2,3-dioxygenase. The presence of DCs with these markers was demonstrated in MF skin lesions. At a molecular level, indoleamine 2,3-dioxygenase messenger RNA (mRNA) levels in MF lesions were higher than those in healthy volunteers, and there was a high correlation between indoleamine 2,3-dioxygenase and IL-32 expression. In contrast, Foxp3 mRNA levels decreased from patch to tumor stage. Increasing expression of IL-10 across MF lesions was highly correlated with IL-32 and indoleamine 2,3-dioxygenase, but not with Foxp3 expression. Thus, IL-32 could contribute to progressive immune dysregulation in MF by directly fostering development of immunosuppressive mDC or macrophages, possibly in association with IL-10.http://dx.doi.org/10.1080/2162402X.2016.1181237cd1c+ dendritic cellscd163+ macrophagesil-32indoleamine 2,3-dioxygenase (ido)mycosis fungoides |
| spellingShingle | Hanako Ohmatsu Daniel Humme Juana Gonzalez Nicholas Gulati Markus Möbs Wolfram Sterry James G. Krueger IL-32 induces indoleamine 2,3-dioxygenase+CD1c+ dendritic cells and indoleamine 2,3-dioxygenase+CD163+ macrophages: Relevance to mycosis fungoides progression OncoImmunology cd1c+ dendritic cells cd163+ macrophages il-32 indoleamine 2,3-dioxygenase (ido) mycosis fungoides |
| title | IL-32 induces indoleamine 2,3-dioxygenase+CD1c+ dendritic cells and indoleamine 2,3-dioxygenase+CD163+ macrophages: Relevance to mycosis fungoides progression |
| title_full | IL-32 induces indoleamine 2,3-dioxygenase+CD1c+ dendritic cells and indoleamine 2,3-dioxygenase+CD163+ macrophages: Relevance to mycosis fungoides progression |
| title_fullStr | IL-32 induces indoleamine 2,3-dioxygenase+CD1c+ dendritic cells and indoleamine 2,3-dioxygenase+CD163+ macrophages: Relevance to mycosis fungoides progression |
| title_full_unstemmed | IL-32 induces indoleamine 2,3-dioxygenase+CD1c+ dendritic cells and indoleamine 2,3-dioxygenase+CD163+ macrophages: Relevance to mycosis fungoides progression |
| title_short | IL-32 induces indoleamine 2,3-dioxygenase+CD1c+ dendritic cells and indoleamine 2,3-dioxygenase+CD163+ macrophages: Relevance to mycosis fungoides progression |
| title_sort | il 32 induces indoleamine 2 3 dioxygenase cd1c dendritic cells and indoleamine 2 3 dioxygenase cd163 macrophages relevance to mycosis fungoides progression |
| topic | cd1c+ dendritic cells cd163+ macrophages il-32 indoleamine 2,3-dioxygenase (ido) mycosis fungoides |
| url | http://dx.doi.org/10.1080/2162402X.2016.1181237 |
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