First Author | Kemp KL | Year | 2013 |
Journal | J Biol Chem | Volume | 288 |
Issue | 46 | Pages | 33272-82 |
PubMed ID | 24100031 | Mgi Jnum | J:205913 |
Mgi Id | MGI:5547425 | Doi | 10.1074/jbc.M113.493171 |
Citation | Kemp KL, et al. (2013) The serine-threonine kinase inositol-requiring enzyme 1alpha (IRE1alpha) promotes IL-4 production in T helper cells. J Biol Chem 288(46):33272-82 |
abstractText | The inositol-requiring enzyme 1alpha (IRE1alpha) is a serine-threonine kinase that plays crucial roles in activating the unfolded protein response. Studies suggest that IRE1alpha 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 IRE1alpha 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 IRE1alpha 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 IRE1alpha KO T cells. Furthermore, treatment of T cells with an IRE1alpha-specific inhibitor, 4mu8C, leads to a block in IL-4, IL-5, and IL-13 production, confirming the role of IRE1alpha in the regulation of IL-4. This study identifies a regulatory function for IRE1alpha in the promotion of IL-4 in T cells. |