Impaired tryptophan metabolism by type 2 inflammation in epithelium worsening asthma
Yushan Miao,
Caiming Zhong,
Shujun Bao,
Kunchen Wei,
Wei Wang,
Na Li,
Chong Bai,
Wei Chen,
Hao Tang
Affiliations
Yushan Miao
Department of Respiratory and Critical Care Medicine, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China; Department of Respiratory and Critical Care Medicine, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China
Caiming Zhong
Department of Respiratory and Critical Care Medicine, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China; Department of Respiratory and Critical Care Medicine, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China
Shujun Bao
Department of Respiratory and Critical Care Medicine, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China
Kunchen Wei
Department of Respiratory and Critical Care Medicine, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China
Wei Wang
Department of Respiratory and Critical Care Medicine, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China
Na Li
School of Medicine, Shanghai University, Shanghai 200444, China
Chong Bai
Department of Respiratory and Critical Care Medicine, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Corresponding author
Wei Chen
Department of Nephrology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Corresponding author
Hao Tang
Department of Respiratory and Critical Care Medicine, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China; Corresponding author
Summary: Previous researches indicate that tryptophan metabolism is critical to allergic inflammation and that indoleamine 2,3-dioxygenase 1 (IDO1), as a key enzyme, is known for its immunosuppressive properties. Therefore, we are aimed to explore whether tryptophan metabolism, especially IDO1, influences allergic asthma and clarify specific mechanism. With the analysis of clinical data, exploration in cell experiments, and verifying in HDM-induced asthma mice models, we finally found that in allergic asthma, low level of T1 cytokines along with high level of T2 cytokines inhibited the expression of IDO1 in airway epithelium, hampering the kynurenine pathway in tryptophan metabolism and decreasing the level of intracellular kynurenine (Kyn). As an endogenous ligand of aryl hydrocarbon receptor, Kyn regulated the expression of cystathionine-γ-lyase (CTH). Notably, in asthma models, enhancing either IDO1 or H2S relieved asthma, while inhibiting the activity of CTH exacerbated it. IDO1-Kyn-CTH pathway could be a potential target for treatment for allergic asthma.
