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 language | English (US) |
|---|---|
| Pages (from-to) | 33272-33282 |
| Number of pages | 11 |
| Journal | Journal of Biological Chemistry |
| Volume | 288 |
| Issue number | 46 |
| DOIs | |
| State | Published - Nov 15 2013 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
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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 journal › Article
TY - JOUR
T1 - The serine-threonine kinase inositol-requiring enzyme 1α (IRE1α) promotes IL-4 production in T helper cells
AU - Kemp, Kyeorda L.
AU - Lin, Zhenghong
AU - Zhao, Fang
AU - Gao, Beixue
AU - Song, Jianxun
AU - Zhang, Kezhong
AU - Fang, Deyu
PY - 2013/11/15
Y1 - 2013/11/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84887853927&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84887853927&partnerID=8YFLogxK
U2 - 10.1074/jbc.M113.493171
DO - 10.1074/jbc.M113.493171
M3 - Article
C2 - 24100031
AN - SCOPUS:84887853927
VL - 288
SP - 33272
EP - 33282
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 46
ER -