E74 Like ETS Transcription Factor 3 is a Negative Regulator of Pathogenic Lamina Propria T Helper 17.1 Cells in Murine Colitis.

Interleukin-17A (IL-17A)-expressing T cells, including T helper 17 (Th17) and T helper 17.1 (Th17.1) cells, play a significant role in inflammatory bowel diseases (IBDs). Identifying the mechanisms underlying the heterogeneity and plasticity of IL-17A-expressing T cells is crucial for understanding and controlling their pathogenicity. The role of E74 like ETS transcription factor 3 (ELF3) in regulating the pathogenicity of IL-17A-expressing T cells has not been studied before. Dextran sulfate sodium was used to induce acute colitis in transgenic mice co-expressing IL-17A and enhanced green fluorescent protein (EGFP). IL-17A-expressing T cells were analyzed by flow cytometry. ELF3 expression was evaluated by reverse transcription and quantitative polymerase chain reaction. Lentivirus-mediated ELF3 overexpression was performed to assess the effect of ELF3 on Th17 and Th17.1 cells in vitro. The in vivo effect of ELF3 on Th17.1 cells was analyzed in an adoptive transfer colitis model. ELF3 was expressed by IL-17A-expressing T cells in the colonic lamina propria after colitis induction. Th17 cells and Th17.1 cells were distinguished based on the expression of C-X-C motif chemokine receptor 3, cytokine production, and key regulators. Th17 cells expressed higher ELF3 than Th17.1 cells. Ectopic ELF3 overexpression did not alter Th17 cell function while suppressing Th17.1 cell function in vitro. When adoptively transferred into Rag1 knockout mice to induce colitis, ELF3-overexpressing Th17.1 cells were less pathogenic than the control Th17.1 cells. ELF3 suppresses the pathogenicity of Th17.1 cells in colitis.