Foxp3+ CD4 Tregs are central regulators of inflammation, including allergic inflammation in the lung. There is increasing evidence that inflammatory factors undermine adequate Treg functions and homeostasis, resulting in prolonged and exacerbated inflammation. Therefore, identifying the factors is of the utmost important. IL-27 is an antiinflammatory cytokine implicated in immune regulation and tolerance. However, the cellular mechanisms underlying IL-27–mediated immune regulation in vivo remain largely unknown. Utilizing a cockroach antigen–induced allergic inflammation model in mice, we sought to test the roles of Tregs during IL-27–mediated regulation of allergic inflammation. Intranasally delivered IL-27 significantly reduced the development of airway inflammation. Unexpectedly, the IL-27–induced reduction occurred only in the presence of Tregs. Il27ra–/– and Treg-specific Il27ra–/– mice developed severe airway inflammation, and IL-27 treatment had little impact on diminishing the inflammatory responses. IL-27–induced treatment was restored following transfer of WT Tregs but not of Tregs deficient in Lag3, a molecule induced by IL-27 in Tregs. Finally, Tregs from asthmatic patients exhibited blunted STAT1 phosphorylation following IL-27 stimulation. Taken together, our results uncover that Tregs are the primary target cells of IL-27 in vivo to mediate its antiinflammatory functions, suggesting that altered IL-27 responsiveness in Tregs may underlie inadequate Treg functions and perpetuation of inflammation.
Quang Tam Nguyen, Eunjung Jang, Hongnga T. Le, Sohee Kim, Dongkyun Kim, Nina Dvorina, Mark A. Aronica, William M. Baldwin III, Kewal Asosingh, Suzy Comhair, Booki Min
Usage data is cumulative from January 2019 through February 2019.
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.