ReferenceID 4740
Bilirubin represents a negative regulator of ILC2 in allergic airway inflammation
Mucosal Immunol
Group 2 innate lymphoid cells (ILC2s) play an important role in allergic airway inflammation. Despite recent advances in defining molecular mechanisms that control ILC2 development and function, the role of endogenous me
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Record Fields
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- Reference Id
- 4740
- Evidence Id
- 21330
- Core Evidence Id
- 21330
- Source Reference Id
- 2721
- Herb2 Reference Id
- HBREF003518
- Subject Paper Key
- HBIN018510_34686839
- Pubmed Id
- 34686839
- Doi
- 10.1038/s41385-021-00460-0
- Paper Title
- Bilirubin represents a negative regulator of ILC2 in allergic airway inflammation
- Paper Abstract
- Group 2 innate lymphoid cells (ILC2s) play an important role in allergic airway inflammation. Despite recent advances in defining molecular mechanisms that control ILC2 development and function, the role of endogenous metabolites in the regulation of ILC2s remains poorly understood. Herein, we demonstrated that bilirubin, an end product of heme catabolism, was a potent negative regulator of ILC2s. Bilirubin metabolism was found to be significantly induced during airway inflammation in mouse models. The administration of unconjugated bilirubin (UCB) dramatically suppressed ILC2 responses to interleukin (IL)-33 in mice, including cell proliferation and the production of effector cytokines. Furthermore, UCB significantly alleviated ILC2-driven airway inflammation, which was aggravated upon clearance of endogenous UCB. Mechanistic studies showed that the effects of bilirubin on ILC2s were associated with downregulation of ERK phosphorylation and GATA3 expression. Clinically, newborns with hyperbilirubinemia displayed significantly lower levels of ILC2 with impaired function and suppressed ERK signaling. Together, these findings indicate that bilirubin serves as an endogenous suppressor of ILC2s and might have potential therapeutic value in the treatment of allergic airway inflammation.
- Journal
- Mucosal Immunol
- Publish Year
- 2022
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Hyperbilirubinemia; Airway Inflammation; Allergic Airway Inflammation
- Paper Title Cn
- Paper Title En
- Bilirubin represents a negative regulator of ILC2 in allergic airway inflammation
- Bilingual Status
- semi_complete