The serine-threonine kinase inositol-requiring enzyme 1α (IRE1α) promotes IL-4 production in T helper cells

Kyeorda L. Kemp, Zhenghong Lin, Fang Zhao, Beixue Gao, Jianxun Song, Kezhong Zhang, Deyu Fang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The inositol-requiring enzyme 1α (IRE1α) is a serine-threonine kinase that plays crucial roles in activating the unfolded protein response. Studies suggest that IRE1α is activated during thymic T cell development and in effector CD8+ T cells. However, its role in regulating T helper cell differentiation remains unknown. We find that IRE1α is up-regulated and activated upon CD4+ T cell activation and plays an important role in promoting cytokine IL-4 production. CD4+ T cells from IRE1α KO mice have reduced IL-4 protein expression, and this impaired IL-4 production is not due to the altered expression of Th2 lineage-specific transcription factors, such as GATA3. Instead, IL-4 mRNA stability is reduced in IRE1α KO T cells. Furthermore, treatment of T cells with an IRE1α-specific inhibitor, 4μ8C, leads to a block in IL-4, IL-5, and IL-13 production, confirming the role of IRE1α in the regulation of IL-4. This study identifies a regulatory function for IRE1α in the promotion of IL-4 in T cells.

Original languageEnglish (US)
Pages (from-to)33272-33282
Number of pages11
JournalJournal of Biological Chemistry
Volume288
Issue number46
DOIs
StatePublished - Nov 15 2013

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Protein-Serine-Threonine Kinases
Inositol
T-cells
Helper-Inducer T-Lymphocytes
Interleukin-4
T-Lymphocytes
Enzymes
Unfolded Protein Response
Interleukin-13
Interleukin-5
RNA Stability
Cell Differentiation
Proteins
Transcription Factors
Chemical activation
Cytokines
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kemp, Kyeorda L. ; Lin, Zhenghong ; Zhao, Fang ; Gao, Beixue ; Song, Jianxun ; Zhang, Kezhong ; Fang, Deyu. / The serine-threonine kinase inositol-requiring enzyme 1α (IRE1α) promotes IL-4 production in T helper cells. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 46. pp. 33272-33282.
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The serine-threonine kinase inositol-requiring enzyme 1α (IRE1α) promotes IL-4 production in T helper cells. / Kemp, Kyeorda L.; Lin, Zhenghong; Zhao, Fang; Gao, Beixue; Song, Jianxun; Zhang, Kezhong; Fang, Deyu.

In: Journal of Biological Chemistry, Vol. 288, No. 46, 15.11.2013, p. 33272-33282.

Research output: Contribution to journalArticle

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