title: Recovery Profiles of T-Cell Subsets Following Low-Dose Total Body Irradiation and Improvement With Cinnamon.
abstract: OBJECTIVE
  Inefficient T-cell reconstitution from x-ray-induced immune damage reduces antitumor response. To understand the profile of T-cell reconstitution after irradiation will overcome the barrier of antitumor immunity. This study aimed to identify the recovery profile of T-cell subsets following x-ray irradiation and to highlight the role of cinnamon on efficient T-cell restoration postexposure in the antitumor response.
  
  
  METHODS
  CD3(+), CD8(+), and CD4(+) T cells and Th1, Th2, Th17, and regulatory T (Treg) cells were evaluated at different time points after single low-dose total body irradiation (SLTBI) with or without cinnamon treatments. T-bet, GATA3, RORγt, and Foxp3 signaling specific for Th1, Th2, Th17, and Treg were also analyzed by RT-PCR assay. The effects of cinnamon on efficient T-cell subset reconstitution was confirmed in a lung melanoma model in irradiated mice.
  
  
  RESULTS
  Reconstitution of CD4(+) T cells was delayed more than that of CD8(+) T cells in T-cell restoration after SLTBI. The production of IFNγ by Th1 or Tc1 cells was sharply decreased and was accompanied by reduced T-bet mRNA, even when total T-cell numbers had recovered; the frequencies of Th17 and Treg cells and their specific transcription factors (RORγt and Foxp3, respectively) were obviously increased. Irradiation-induced inefficient T-cell reconstitution impaired the antitumor capacities in the lung melanoma model. Pretreatment with cinnamon in irradiated mice accelerated the generation of Th1 and reduced the differentiation of Treg cells by activating T-bet and limiting transcriptions of Foxp3. Improvement resulting from cinnamon pretreatment on the efficient T-cell recovery profile from SLTBI promoted antitumor immunity in the lung melanoma model.
  
  
  CONCLUSIONS
  T-cell reconstitution from SLTBI was characterized by impaired Th1 and elevated Th17 and Treg cells. Cinnamon effectively improved the imbalance of T-cell subsets by promoting the proliferation of Th1 and by suppressing expansions of Th17 and Tregs. The role of cinnamon in efficient T-cell reconstitution from SLTBI is effective in antitumor immunity.
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China; School of Medicine and Life Science, University of Jinan-Shandong Academy of Medical Science, Jinan, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Shandong University, Jinan, China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China; School of Medicine and Life Science, University of Jinan-Shandong Academy of Medical Science, Jinan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: An
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Xianbin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China. Electronic address: yaocf9941@163.com.
authors.forename: Chengfang
authors.initials: C
authors.lastname: Yao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002935:Cinnamomum zeylanicum; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism; D007111:Immunity, Cellular / Q000528:radiation effects; D007371:Interferon-gamma / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012318:RNA Polymerase I; D012333:RNA, Messenger / Q000378:metabolism; D011879:Radiotherapy Dosage; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D000098815:T-bet Transcription Factor
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; D047908:Intracellular Signaling Peptides and Proteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010936:Plant Extracts; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma; C119975:POLR1G protein, human; D012318:RNA Polymerase I