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Transcriptional Profiling of Non-Human Primate Lymphoid Organ Responses to Total-Body Irradiation.

  • Academic Journal
  • Caudell DL; a Departments of Pathology, Section on Comparative Medicine.
    Michalson KT; a Departments of Pathology, Section on Comparative Medicine.
    Andrews RN; a Departments of Pathology, Section on Comparative Medicine.
    Snow WW; a Departments of Pathology, Section on Comparative Medicine.
    Bourland JD; b Departments of Radiation Oncology, Wake Forest School of Medicine, Winston Salem, North Carolina.
    DeBo RJ; a Departments of Pathology, Section on Comparative Medicine.
    Cline JM; a Departments of Pathology, Section on Comparative Medicine.
    Sempowski GD; c Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
    Register TC; a Departments of Pathology, Section on Comparative Medicine.
  • Radiation research [Radiat Res] 2019 Jul; Vol. 192 (1), pp. 40-52. Date of Electronic Publication: 2019 May 06.
  • English
  • The global threat of exposure to radiation and its subsequent outcomes require the development of effective strategies to mitigate immune cell injury. In this study we explored transcriptional and immunophenotypic characteristics of lymphoid organs of a non-human primate model after total-body irradiation (TBI). Fifteen middle-aged adult, ovariectomized, female cynomolgus macaques received a single dose of 0, 2 or 5 Gy gamma radiation. Thymus, spleen and lymph node from three controls and 2 Gy (n = 2) and 5 Gy (n = 2) exposed animals were assessed for molecular responses to TBI through microarray-based transcriptional profiling at day 5 postirradiation, and cellular changes through immunohistochemical (IHC) characterization of markers for B and T lymphocytes and macrophages across all 15 animals at time points up to 6 months postirradiation. Irradiated macaques developed acute hematopoietic syndrome. Analysis of array data at day 5 postirradiation identified transcripts with ≥2-fold difference from control and a false discovery rate (FDR) of P adj < 0.05 in lymph node (n = 666), spleen (n = 493) and thymus (n=3,014). Increasing stringency of the FDR to P < 0.001 reduced the number of genes to 71 for spleen and 379 for thymus. IHC and gene expression data demonstrated that irradiated animals had reduced numbers of T and B lymphocytes along with relative elevations of macrophages. Transcriptional analysis revealed unique patterns in primary and secondary lymphoid organs of cynomolgus macaques. Among the many differentially regulated transcripts, upregulation of noncoding RNAs [ MIR34A for spleen and thymus and NEAT1 ( NCRNA00084 ) for thymus] showed potential as biomarkers of radiation injury and targets for mitigating the effects of radiation-induced hematopoietic syndrome-impaired lymphoid reconstitution.
Additional Information
Publisher: Radiation Research Society Country of Publication: United States NLM ID: 0401245 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1938-5404 (Electronic) Linking ISSN: 00337587 NLM ISO Abbreviation: Radiat Res Subsets: MEDLINE
Publication: Bozeman, MT : Radiation Research Society
Original Publication: Charlottesville, VA : Kluge Carden Jennnings Pub. Co.
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P30 CA012197 United States CA NCI NIH HHS; T32 OD010957 United States OD NIH HHS; U19 AI067798 United States AI NIAID NIH HHS; UC6 AI058607 United States AI NIAID NIH HHS
Date Created: 20190507 Date Completed: 20191018 Latest Revision: 20210417