2. Academic Validation
  3. Bilirubin represents a negative regulator of ILC2 in allergic airway inflammation

Bilirubin represents a negative regulator of ILC2 in allergic airway inflammation

  • Mucosal Immunol. 2022 Feb;15(2):314-326. doi: 10.1038/s41385-021-00460-0.
Juan He  # 1 2,  Guanmin Jiang  # 3,  Xing Li  # 4,  Qiang Xiao 2 3,  Yingying Chen 1 2,  Haixu Xu 2,  Gaoyu Liu 1 2,  Aihua Lei 1,  Pan Zhou 2,  Kun Shi 5,  Quan Yang 6,  Meng Zhao 7,  Zhi Yao 8,  Jie Zhou 9 10
Affiliations

Affiliations

  • 1 Joint Program in Immunology, Department of Internal Medicine, Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 2 Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • 3 Department of Clinical laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
  • 4 The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • 5 Department of Obstetrics and Gynaecology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
  • 6 Key Laboratory of Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences; Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
  • 7 Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
  • 8 Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. [email protected].
  • 9 Joint Program in Immunology, Department of Internal Medicine, Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. [email protected].
  • 10 Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. [email protected].
  • # Contributed equally.
PMID: 34686839 DOI: 10.1038/s41385-021-00460-0
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.

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