Cell-autonomous iodothyronine deiodinase expression mediates seasonal plasticity in immune function.

Tyler J. Stevenson, Kenneth G. Onishi, Sean P. Bradley, Brian J. Prendergast

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Annual rhythms in morbidity and mortality are well-documented, and host defense mechanisms undergo marked seasonal phenotypic change. Siberian hamsters (Phodopus sungorus) exhibit striking immunological plasticity following adaptation to short winter day lengths (SD), including increases in blood leukocytes and in the magnitude of T cell-mediated immune responses. Thyroid hormone (TH) signaling is rate-limited by tissue-level expression of iodothyronine deiodinase types II and III (dio2, dio3), and dio2/dio3 expression in the central nervous system gate TH-dependent transduction of photoperiod information into the neuroendocrine system. THs are also potent immunomodulators, but their role in seasonal immunobiology remains unexamined. Here we report that photoperiod-driven changes in triiodothyronine (T3) signaling mediate seasonal changes in multiple aspects of immune function. Transfer from long days (LD) to SD inhibited leukocyte dio3 expression, which increased cellular T4→T3 catabolism. T3 was preferentially localized in the lymphocyte cytoplasm, consistent with a non-nuclear role of T3 in lymphoid cell differentiation and maturation. Exposure to SD upregulated leukocyte DNA methyltransferase expression and markedly increased DNA methylation in the dio3 proximal promoter region. Lastly, to bypass low endogenous T3 biosynthesis in LD lymphocytes, LD hamsters were treated with T3, which enhanced T cell-dependent delayed-type hypersensitivity inflammatory responses and blood leukocyte concentrations in a dose-dependent manner, mimicking effects of SD on these immunophenotypes. T3 signaling represents a novel mechanism by which environmental day length cues impact the immune system: changes in day length alter lymphoid cell T3-signaling via epigenetic transcriptional control of dio3 expression.
Original languageEnglish
Pages (from-to)61-70
Number of pages10
JournalBrain, Behavior, and Immunity
Early online date19 Oct 2013
Publication statusPublished - Feb 2014

Bibliographical note

The authors thank Drs. Betty Theriault and Priyesh Patel for expert technical assistance, and the University of Chicago Comprehensive Cancer Center DNA Sequencing and Genotyping Facility for sequencing instrumentation and expertise. This work was funded by grant NIH NIAID AI-67406 and by NIH grant UL1 TR000430 from the National Center for Advancing Translational Sciences.


  • Thyroid
  • Photoperiod
  • Hamster
  • Cytometry
  • Rhythm
  • Adaptive immunity
  • Imaging flow cytometry


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