Dynamic regulation of T h17 differentiation by oxygen concentrations

Ai Ikejiri, Shigenori Nagai, Nobuhito Goda, Yutaka Kurebayashi, Mayuko Osada-Oka, Keiyo Takubo, Toshio Suda, Shigeo Koyasu

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


Naive CD4 + T cells are activated by antigen-presenting cells (APCs) and differentiate into distinct types of helper T (T h) cells in the lymph node or spleen. Oxygen (O 2) tension is generally low in these secondary lymphoid tissues compared with the bloodstream or atmosphere. However, the effect of changes in O 2 concentration on the differentiation of T h cells remains unclear. Here, we established a novel model of T h-cell differentiation, which mimics physiological O 2 conditions. We primed naive CD4 + T cells under 5% O 2, which has been observed in the lymph node or spleen and reoxygenated under normoxia that mimicked the O 2 concentration in blood. In this model, the differentiation of T h17 cells, but not T h1 or iTreg cells, was enhanced. Under the condition of 5% O 2, mammalian target of rapamycin complex 1 (mTORC1) was activated and led to the stabilization of hypoxia-inducible factor 1α (HIF-1α) in T h17 cells. The activation of mTORC1 and the acceleration of T h17-cell differentiation, which occurred when cells were primed under 5% O 2, were not observed in the absence of HIF-1α but were accelerated in the absence of von Hippel-Lindau tumor suppressor protein (vHL), a factor critical for HIF-1α degradation. Thus, a positive feedback loop between HIF-1α and mTORC1 induced by hypoxia followed by reoxygenation accelerates T h17-cell differentiation.

Original languageEnglish
Pages (from-to)137-146
Number of pages10
JournalInternational immunology
Issue number3
Publication statusPublished - 2012


  • HIF-1α
  • IL-17
  • Reoxygenation
  • mTORC1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Dynamic regulation of T <sub>h</sub>17 differentiation by oxygen concentrations'. Together they form a unique fingerprint.

Cite this