Capacity of tTreg generation is not impaired in the atrophied thymus

Jiyoung Oh, Weikan Wang, Rachel Thomas, Dong Ming Su

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

Postnatal thymic epithelial cell (TEC) homeostatic defect- or natural aging-induced thymic atrophy results in a decline in central T-cell tolerance establishment, which is constituted by thymocyte negative selection and cluster of differentiation (CD) 4+thymic regulatory T (tTreg) cell generation. Emerging evidence shows this decline mainly results from defects in negative selection, but there is insufficient evidence regarding whether tTreg cell generation is also impaired. We mechanistically studied tTreg cell generation in the atrophied thymus by utilizing both postnatal TEC-defective (resulting from FoxN1-floxed conditional knockout [cKO]) and naturally aged mouse models. We found that the capacity of tTreg cell generation was not impaired compared to CD4+thymic conventional T cells, suggesting thymic atrophy positively influences tTreg cell generation. This is potentially attributed to decreased T cell receptor (TCR) signaling strength due to inefficiency in promiscuous expression of self-antigens or presenting a neo-self-antigen by medullary TECs, displaying decreased negative selection-related marker genes (Nur77 and CD5high) in CD4 single positive (SP) thymocytes. Our results provide evidence that the atrophied thymus attempts to balance the defective negative selection by enhancing tTreg cell generation to maintain central T-cell tolerance in the elderly. Once the balance is broken, age-related diseases could take place.

Original languageEnglish
Article numbere2003352
JournalPLoS Biology
Volume15
Issue number11
DOIs
StatePublished - 8 Nov 2017

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Thymus
T-cells
Thymus Gland
T-lymphocytes
Autoantigens
thymocytes
Thymocytes
Defects
atrophy
T-Lymphocytes
Atrophy
cells
T-Cell Antigen Receptor
epithelial cells
Epithelial Cells
antigens
Genes
Aging of materials
Regulatory T-Lymphocytes
animal models

Cite this

Oh, Jiyoung ; Wang, Weikan ; Thomas, Rachel ; Su, Dong Ming. / Capacity of tTreg generation is not impaired in the atrophied thymus. In: PLoS Biology. 2017 ; Vol. 15, No. 11.
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abstract = "Postnatal thymic epithelial cell (TEC) homeostatic defect- or natural aging-induced thymic atrophy results in a decline in central T-cell tolerance establishment, which is constituted by thymocyte negative selection and cluster of differentiation (CD) 4+thymic regulatory T (tTreg) cell generation. Emerging evidence shows this decline mainly results from defects in negative selection, but there is insufficient evidence regarding whether tTreg cell generation is also impaired. We mechanistically studied tTreg cell generation in the atrophied thymus by utilizing both postnatal TEC-defective (resulting from FoxN1-floxed conditional knockout [cKO]) and naturally aged mouse models. We found that the capacity of tTreg cell generation was not impaired compared to CD4+thymic conventional T cells, suggesting thymic atrophy positively influences tTreg cell generation. This is potentially attributed to decreased T cell receptor (TCR) signaling strength due to inefficiency in promiscuous expression of self-antigens or presenting a neo-self-antigen by medullary TECs, displaying decreased negative selection-related marker genes (Nur77 and CD5high) in CD4 single positive (SP) thymocytes. Our results provide evidence that the atrophied thymus attempts to balance the defective negative selection by enhancing tTreg cell generation to maintain central T-cell tolerance in the elderly. Once the balance is broken, age-related diseases could take place.",
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Capacity of tTreg generation is not impaired in the atrophied thymus. / Oh, Jiyoung; Wang, Weikan; Thomas, Rachel; Su, Dong Ming.

In: PLoS Biology, Vol. 15, No. 11, e2003352, 08.11.2017.

Research output: Contribution to journalArticleResearchpeer-review

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