Two major CD4+ T-helper (Th) lineages are Th1 and Th2, and well balanced Th1/Th2 responses are essential for immune function. In previously published studies, it was reported that radiation induces a Th1/Th2 immune imbalance toward a Th2-dominant direction, and this imbalance may contribute to postirradiation immune dysfunction. The polarization of Th cells is driven by the cytokine milieu and controlled by intracellular regulatory pathways that respond to cytokine signaling. It is widely accepted that radiation induces cytokine aberration, however, the precise alterations of cytokines in various tissue environments have been difficult to evaluate. In addition, the effects of radiation on the intrinsic functions of Th cells remain uncharacterized. Therefore, how radiation affects Th1/Th2 balance remains somewhat unclear. To address this, we investigated the changes in the polarization capability of Th cells by isolating them from mice previously exposed to radiation and assessing the cells in an established in vitro Th polarization system. Our novel results demonstrate that prior exposure to radiation led to the persistent aberration of the inherent capability of Th cells to differentiate into Th1 and Th2 lineages. The parallel changes in expression of Th1-specific master transcription factors and the key genes in metabolic reprograming indicated that radiation affects the core components in Th1 polarization. While Th1 differentiation was impaired after irradiation, little adverse effect was observed in Th2 differentiation; both of these findings contribute to the known phenotypes of Th1/Th2 imbalance caused by radiation.
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1 December 2016
Research Article|
November 16 2016
Impairment of the Intrinsic Capability of Th1 Polarization in Irradiated Mice: A Close Look at the Imbalanced Th1/Th2 Response after Irradiation
Renxiang Chen
;
Renxiang Chen
aDepartment of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, D.C. 20057
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Yi-wen Wang
;
Yi-wen Wang
aDepartment of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, D.C. 20057
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Albert J. Fornace, Jr.
;
Albert J. Fornace, Jr.
aDepartment of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, D.C. 20057
bDepartment of Oncology, Georgetown University Medical Center, Washington, D.C. 20057
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Heng-Hong Li
Heng-Hong Li
1
aDepartment of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, D.C. 20057
bDepartment of Oncology, Georgetown University Medical Center, Washington, D.C. 20057
1Address for correspondence: Georgetown University, Department of Biochemistry and Molecular and Cellular Biology, 3970 Reservoir Rd, NW, New Research Building, Room E518, Washington DC, 20057; email: hl234@georgetown.edu
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Radiat Res (2016) 186 (6): 559–567.
Citation
Renxiang Chen, Yi-wen Wang, Albert J. Fornace, Heng-Hong Li; Impairment of the Intrinsic Capability of Th1 Polarization in Irradiated Mice: A Close Look at the Imbalanced Th1/Th2 Response after Irradiation. Radiat Res 1 December 2016; 186 (6): 559–567. doi: https://doi.org/10.1667/RR14401.1
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