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 journalArticle

34 Citations (Scopus)

Abstract

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
Volume24
Issue number3
DOIs
Publication statusPublished - 2012

Fingerprint

Hypoxia-Inducible Factor 1
Oxygen
Cell Differentiation
Von Hippel-Lindau Tumor Suppressor Protein
Spleen
Lymph Nodes
T-Lymphocytes
Lymphoid Tissue
Antigen-Presenting Cells
Atmosphere
mechanistic target of rapamycin complex 1

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Ikejiri, A., Nagai, S., Goda, N., Kurebayashi, Y., Osada-Oka, M., Takubo, K., ... Koyasu, S. (2012). Dynamic regulation of T h17 differentiation by oxygen concentrations. International Immunology, 24(3), 137-146. https://doi.org/10.1093/intimm/dxr111

Dynamic regulation of T h17 differentiation by oxygen concentrations. / Ikejiri, Ai; Nagai, Shigenori; Goda, Nobuhito; Kurebayashi, Yutaka; Osada-Oka, Mayuko; Takubo, Keiyo; Suda, Toshio; Koyasu, Shigeo.

In: International Immunology, Vol. 24, No. 3, 2012, p. 137-146.

Research output: Contribution to journalArticle

Ikejiri, A, Nagai, S, Goda, N, Kurebayashi, Y, Osada-Oka, M, Takubo, K, Suda, T & Koyasu, S 2012, 'Dynamic regulation of T h17 differentiation by oxygen concentrations', International Immunology, vol. 24, no. 3, pp. 137-146. https://doi.org/10.1093/intimm/dxr111
Ikejiri A, Nagai S, Goda N, Kurebayashi Y, Osada-Oka M, Takubo K et al. Dynamic regulation of T h17 differentiation by oxygen concentrations. International Immunology. 2012;24(3):137-146. https://doi.org/10.1093/intimm/dxr111
Ikejiri, Ai ; Nagai, Shigenori ; Goda, Nobuhito ; Kurebayashi, Yutaka ; Osada-Oka, Mayuko ; Takubo, Keiyo ; Suda, Toshio ; Koyasu, Shigeo. / Dynamic regulation of T h17 differentiation by oxygen concentrations. In: International Immunology. 2012 ; Vol. 24, No. 3. pp. 137-146.
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