Drug screening identifies pyrrolidinedithiocarbamate ammonium ameliorating DSS-induced mouse ulcerative colitis via suppressing Th17 differentiation

Yu-E Guo; Jie Lv; Ping Shu; Xi Li; Ying Li; Junhong Guo; Guofang Chen; Yuping Li; Bo Lu; Wei Zhang; Yin Liu

doi:10.1016/j.cellimm.2024.104887

Drug screening identifies pyrrolidinedithiocarbamate ammonium ameliorating DSS-induced mouse ulcerative colitis via suppressing Th17 differentiation

Cell Immunol. 2024 Oct 22:405-406:104887. doi: 10.1016/j.cellimm.2024.104887. Online ahead of print.

Authors

Yu-E Guo¹, Jie Lv², Ping Shu¹, Xi Li¹, Ying Li¹, Junhong Guo³, Guofang Chen⁴, Yuping Li¹, Bo Lu⁵, Wei Zhang⁶, Yin Liu⁷

Affiliations

¹ Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
³ Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
⁴ Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
⁵ Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: [email protected].
⁶ Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: [email protected].
⁷ Department of Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: [email protected].

PMID: 39503083
DOI: 10.1016/j.cellimm.2024.104887

Abstract

T helper 17 (Th17) cells play crucial roles in various autoimmune diseases, including ulcerative colitis (UC), which is characterized by widespread inflammation in the mucosa of the colon and rectum. To identify small-molecule compounds capable of inhibiting CD4⁺ T cell differentiation into Th17 cells, we established a screening system. Through drug screening, we found that pyrrolidinedithiocarbamate ammonium (PDTC) effectively inhibits Th17 differentiation. In a dextran sulfate sodium (DSS)-induced UC mouse model, administration of PDTC significantly ameliorated colitis. PDTC treatment decreased the production of proinflammatory mediators and inhibited the proportion of Th17 cells in colitis-afflicted mice by suppressing NF-κB activation. These findings showed that PDTC can alleviate colitis by inhibiting NF-κB activation. The therapeutic effects of PDTC observed in a mouse model of UC provided a rationale for its application in clinical settings.

Keywords: Differentiation; Drug screening; PDTC ameliorates colitis; Pyrrolidinedithiocarbamate ammonium (PDTC); Th17 cells; Ulcerative colitis.