The immune system is capable of mounting robust responses against invading pathogens but refrains from attacking self. Many studies have focused on tolerance induction of Th1 cells, whose failure results in development of autoimmune diseases. However, the molecular mechanisms governing tolerance induction in Th2 cells and its relation to allergic responses remain unclear. Here we used both in vivo and in vitro protocols to demonstrate that Th2 cells either containing a mitogen and extracellular kinase kinase 1 (MEKK1) mutant or lacking JNK1 or the E3 ubiquitin ligase Itch cannot be tolerized. In a mouse allergic model, injection of high-dose tolerizing antigen failed to block the development of airway inflammation in Itch–/– mice. This study suggests that MEKK1-JNK signaling regulates Itch E3 ligase–mediated tolerogenic process in Th2 cells. These findings have therapeutic implications for allergic diseases.
K. Venuprasad, Chris Elly, Min Gao, Shahram Salek-Ardakani, Yohsuke Harada, Jun-Li Luo, Chun Yang, Michael Croft, Kazushi Inoue, Michael Karin, Yun-Cai Liu
Usage data is cumulative from May 2023 through May 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 183 | 20 |
53 | 15 | |
Figure | 99 | 12 |
Supplemental data | 10 | 0 |
Citation downloads | 8 | 0 |
Totals | 353 | 47 |
Total Views | 400 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.