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Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability
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| Zeitschriftentitel: | The Journal of Immunology |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | The Journal of Immunology, 198, 2017, 7, S. 2612-2625 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The American Association of Immunologists
|
| Schlagwörter: |
| author_facet |
Zhang, Zhongmei Zhang, Wei Guo, Jie Gu, Qianchong Zhu, Xueping Zhou, Xuyu Zhang, Zhongmei Zhang, Wei Guo, Jie Gu, Qianchong Zhu, Xueping Zhou, Xuyu |
|---|---|
| author |
Zhang, Zhongmei Zhang, Wei Guo, Jie Gu, Qianchong Zhu, Xueping Zhou, Xuyu |
| spellingShingle |
Zhang, Zhongmei Zhang, Wei Guo, Jie Gu, Qianchong Zhu, Xueping Zhou, Xuyu The Journal of Immunology Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability Immunology Immunology and Allergy |
| author_sort |
zhang, zhongmei |
| spelling |
Zhang, Zhongmei Zhang, Wei Guo, Jie Gu, Qianchong Zhu, Xueping Zhou, Xuyu 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.1601409 <jats:title>Abstract</jats:title> <jats:p>Accumulating evidence suggests that Foxp3+ cells can downregulate the expression of Foxp3, but whether thymically derived regulatory T cells (tTregs; especially committed tTregs) are capable of downregulating Foxp3 expression and being reprogrammed into other T effector cells remains controversial. Using a novel tTreg lineage-tracing mouse line, we were able to label epigenetically stable Foxp3+ cells derived from the thymus and demonstrate that mature tTregs are stable under homeostatic conditions. However, TCR engagement and sequential functional specialization of tTregs led to the generation of Foxp3 instability and reprogramming into the Th lineage. We further demonstrated that the signal switch from IL-2 to ICOS during Treg activation induced Treg instability and reprogramming. By using a dual lineage tracing model, we demonstrated that effector Tregs can revert to central Tregs, and this reversion is associated with increasing Foxp3 stability in vivo.</jats:p> Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability The Journal of Immunology |
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The American Association of Immunologists, 2017 |
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The American Association of Immunologists, 2017 |
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The Journal of Immunology |
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| title |
Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability |
| title_unstemmed |
Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability |
| title_full |
Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability |
| title_fullStr |
Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability |
| title_full_unstemmed |
Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability |
| title_short |
Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability |
| title_sort |
activation and functional specialization of regulatory t cells lead to the generation of foxp3 instability |
| topic |
Immunology Immunology and Allergy |
| url |
http://dx.doi.org/10.4049/jimmunol.1601409 |
| publishDate |
2017 |
| physical |
2612-2625 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Accumulating evidence suggests that Foxp3+ cells can downregulate the expression of Foxp3, but whether thymically derived regulatory T cells (tTregs; especially committed tTregs) are capable of downregulating Foxp3 expression and being reprogrammed into other T effector cells remains controversial. Using a novel tTreg lineage-tracing mouse line, we were able to label epigenetically stable Foxp3+ cells derived from the thymus and demonstrate that mature tTregs are stable under homeostatic conditions. However, TCR engagement and sequential functional specialization of tTregs led to the generation of Foxp3 instability and reprogramming into the Th lineage. We further demonstrated that the signal switch from IL-2 to ICOS during Treg activation induced Treg instability and reprogramming. By using a dual lineage tracing model, we demonstrated that effector Tregs can revert to central Tregs, and this reversion is associated with increasing Foxp3 stability in vivo.</jats:p> |
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| author | Zhang, Zhongmei, Zhang, Wei, Guo, Jie, Gu, Qianchong, Zhu, Xueping, Zhou, Xuyu |
| author_facet | Zhang, Zhongmei, Zhang, Wei, Guo, Jie, Gu, Qianchong, Zhu, Xueping, Zhou, Xuyu, Zhang, Zhongmei, Zhang, Wei, Guo, Jie, Gu, Qianchong, Zhu, Xueping, Zhou, Xuyu |
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| description | <jats:title>Abstract</jats:title> <jats:p>Accumulating evidence suggests that Foxp3+ cells can downregulate the expression of Foxp3, but whether thymically derived regulatory T cells (tTregs; especially committed tTregs) are capable of downregulating Foxp3 expression and being reprogrammed into other T effector cells remains controversial. Using a novel tTreg lineage-tracing mouse line, we were able to label epigenetically stable Foxp3+ cells derived from the thymus and demonstrate that mature tTregs are stable under homeostatic conditions. However, TCR engagement and sequential functional specialization of tTregs led to the generation of Foxp3 instability and reprogramming into the Th lineage. We further demonstrated that the signal switch from IL-2 to ICOS during Treg activation induced Treg instability and reprogramming. By using a dual lineage tracing model, we demonstrated that effector Tregs can revert to central Tregs, and this reversion is associated with increasing Foxp3 stability in vivo.</jats:p> |
| doi_str_mv | 10.4049/jimmunol.1601409 |
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| imprint | The American Association of Immunologists, 2017 |
| imprint_str_mv | The American Association of Immunologists, 2017 |
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| physical | 2612-2625 |
| publishDate | 2017 |
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| spelling | Zhang, Zhongmei Zhang, Wei Guo, Jie Gu, Qianchong Zhu, Xueping Zhou, Xuyu 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.1601409 <jats:title>Abstract</jats:title> <jats:p>Accumulating evidence suggests that Foxp3+ cells can downregulate the expression of Foxp3, but whether thymically derived regulatory T cells (tTregs; especially committed tTregs) are capable of downregulating Foxp3 expression and being reprogrammed into other T effector cells remains controversial. Using a novel tTreg lineage-tracing mouse line, we were able to label epigenetically stable Foxp3+ cells derived from the thymus and demonstrate that mature tTregs are stable under homeostatic conditions. However, TCR engagement and sequential functional specialization of tTregs led to the generation of Foxp3 instability and reprogramming into the Th lineage. We further demonstrated that the signal switch from IL-2 to ICOS during Treg activation induced Treg instability and reprogramming. By using a dual lineage tracing model, we demonstrated that effector Tregs can revert to central Tregs, and this reversion is associated with increasing Foxp3 stability in vivo.</jats:p> Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability The Journal of Immunology |
| spellingShingle | Zhang, Zhongmei, Zhang, Wei, Guo, Jie, Gu, Qianchong, Zhu, Xueping, Zhou, Xuyu, The Journal of Immunology, Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability, Immunology, Immunology and Allergy |
| title | Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability |
| title_full | Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability |
| title_fullStr | Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability |
| title_full_unstemmed | Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability |
| title_short | Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability |
| title_sort | activation and functional specialization of regulatory t cells lead to the generation of foxp3 instability |
| title_unstemmed | Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability |
| topic | Immunology, Immunology and Allergy |
| url | http://dx.doi.org/10.4049/jimmunol.1601409 |