The Loss of H3K27 Histone Demethylase Utx in T Cells Aggravates Allergic Contact Dermatitis
Copyright © 2021 by The American Association of Immunologists, Inc..
The pathogenesis of allergic contact dermatitis (ACD) requires the activation of Ag-specific T cells, including effector and regulatory T cells. The differentiation and function of these T cells is epigenetically regulated through DNA methylation and histone modifications. However, the roles of altered histone H3K27 methylation in T cells in the development of ACD remain unknown. Two types of histone H3K27 demethylases, Utx and Jmjd3, have been reported in mammals. To determine the role of the histone H3K27 demethylase expression of T cells in the development of ACD, we generated T cell-specific, Utx-deficient (Utx KO) mice or Jmjd3-deficient (Jmjd3 KO) mice. Unlike control mice, Utx KO mice had severer symptoms of ACD, whereas Jmjd3 KO mice showed symptoms identical to those in control mice. In Utx KO mice with ACD, the massive infiltration of myeloid cells, including neutrophils and dendritic cells, has been observed. In addition, the expression of proinflammatory cytokines in CD4+ T cells of the draining lymph nodes (LNs) and in CD8+ T cells of the skin was increased in Utx KO mice, whereas the ratio of Foxp3+ regulatory CD4+ T cells to Foxp3- conventional CD4+ T cells was decreased in both the draining LNs and the skin of Utx KO mice with ACD. Furthermore, Foxp3+ regulatory CD4+ T cells of Utx KO mice with ACD expressed a decreased level of CCR4 (a skin-tropic chemokine receptor) in comparison with control. Thus, in CD4+ T cells, Utx could potentially be involved in the regulation of the pathogenesis of ACD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:207 |
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| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 207(2021), 9 vom: 01. Nov., Seite 2223-2234 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Inoue, Takashi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.11.2021 Date Revised 08.11.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4049/jimmunol.2001160 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM331297167 |
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| 100 | 1 | |a Inoue, Takashi |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The Loss of H3K27 Histone Demethylase Utx in T Cells Aggravates Allergic Contact Dermatitis |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 08.11.2021 | ||
| 500 | |a Date Revised 08.11.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 by The American Association of Immunologists, Inc. | ||
| 520 | |a The pathogenesis of allergic contact dermatitis (ACD) requires the activation of Ag-specific T cells, including effector and regulatory T cells. The differentiation and function of these T cells is epigenetically regulated through DNA methylation and histone modifications. However, the roles of altered histone H3K27 methylation in T cells in the development of ACD remain unknown. Two types of histone H3K27 demethylases, Utx and Jmjd3, have been reported in mammals. To determine the role of the histone H3K27 demethylase expression of T cells in the development of ACD, we generated T cell-specific, Utx-deficient (Utx KO) mice or Jmjd3-deficient (Jmjd3 KO) mice. Unlike control mice, Utx KO mice had severer symptoms of ACD, whereas Jmjd3 KO mice showed symptoms identical to those in control mice. In Utx KO mice with ACD, the massive infiltration of myeloid cells, including neutrophils and dendritic cells, has been observed. In addition, the expression of proinflammatory cytokines in CD4+ T cells of the draining lymph nodes (LNs) and in CD8+ T cells of the skin was increased in Utx KO mice, whereas the ratio of Foxp3+ regulatory CD4+ T cells to Foxp3- conventional CD4+ T cells was decreased in both the draining LNs and the skin of Utx KO mice with ACD. Furthermore, Foxp3+ regulatory CD4+ T cells of Utx KO mice with ACD expressed a decreased level of CCR4 (a skin-tropic chemokine receptor) in comparison with control. Thus, in CD4+ T cells, Utx could potentially be involved in the regulation of the pathogenesis of ACD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Ccr4 protein, mouse |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a FOXP3 protein, human |2 NLM | |
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| 650 | 7 | |a EC 1.14.11.- |2 NLM | |
| 650 | 7 | |a Kdm6b protein, mouse |2 NLM | |
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| 700 | 1 | |a Omori-Miyake, Miyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Maruyama, Saho |e verfasserin |4 aut | |
| 700 | 1 | |a Okabe, Masataka |e verfasserin |4 aut | |
| 700 | 1 | |a Kuwahara, Makoto |e verfasserin |4 aut | |
| 700 | 1 | |a Honda, Hiroaki |e verfasserin |4 aut | |
| 700 | 1 | |a Miura, Hiromasa |e verfasserin |4 aut | |
| 700 | 1 | |a Yamashita, Masakatsu |e verfasserin |4 aut | |
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