Advertisement

 

 

Palmitate inhibits arthritis by inducing t-bet and gata-3 mRNA degradation in iNKT cells via IRE1α-dependent decay.

Palmitate inhibits arthritis by inducing t-bet and gata-3 mRNA degradation in iNKT cells via IRE1α-dependent decay.
Author Information (click to view)

Ko JS, Koh JM, So JS, Jeon YK, Kim HY, Chung DH,


Ko JS, Koh JM, So JS, Jeon YK, Kim HY, Chung DH, (click to view)

Ko JS, Koh JM, So JS, Jeon YK, Kim HY, Chung DH,

Advertisement

Scientific reports 2017 11 027(1) 14940 doi 10.1038/s41598-017-14780-4
Abstract

Long chain fatty acids (LCFAs) exert pro-inflammatory effects in vivo. However, little is known regarding the effect of LCFAs on invariant (i) NKT cell functions. Here, we report an inhibitory effect of saturated LCFAs on transcription factors in iNKT cells. Among the saturated LCFAs, palmitic acid (PA) specifically inhibited IL-4 and IFN-γ production and reduced gata-3 and t-bet transcript levels in iNKT cells during TCR-mediated activation. In iNKT cells, PA was localized and induced dilation in the endoplasmic reticulum and increased the mRNA levels of downstream molecules of IRE1α RNase. Moreover, PA increased the degradation rates of gata-3 and t-bet mRNA, which was restored by IRE1α inhibition or transfection with mutant gata-3 or t-bet, indicating that gata-3 and t-bet are cleaved via regulated IRE1α-dependent decay (RIDD). A PA-rich diet and PA injection suppressed IL-4 and IFN-γ production by iNKT cells in C57BL/6, but not Jα18 knockout mice, which was restored by injection of STF083010, an IRE1α-specific inhibitor. Furthermore, a PA-rich diet and PA injection attenuated arthritis in an iNKT cell-dependent manner. Taken together, our experiments demonstrate that a saturated LCFA induced RIDD-mediated t-bet and gata-3 mRNA degradation in iNKT cells, thereby suppressing arthritis.

Submit a Comment

Your email address will not be published. Required fields are marked *

eight + 3 =

[ HIDE/SHOW ]