ETS2 is a transcription factor that binds to enhancers as part of the signaling pathway, thus increasing gene transcription. And the genes that ETS2 can regulate are tricky, the research shows: By studying genome-wide association, among other things, the research group realized that genetic variants in genes regulated by ETS2 are associated with an increased risk of Crohn's disease and peptic ulcers. Colitis. Nearly 75 percent of Europeans and more than 90 percent of Africans carry the ETS2 risk allele. Other inflammatory diseases have also been linked to ETS2-regulated genes: primary sclerosing cholangitis, Takayasu's arteritis, and ankylosing spondylitis, occurring statistically more frequently with certain genetic variants that are activated via ETS2.
To investigate the function of ETS2, the research group examined macrophages that over- or under-expressed the transcription factor. Thus almost all inflammatory functions of macrophages are regulated by ETS2. Production of cytokines known to be involved in IBD, such as tumor necrosis factors (TNF) or interleukin (IL)-23, was also affected in ETS2 analyses. In addition, some already known risk genes for IBD are read through the ETS2 signaling pathway. Macrophages overexpressing ETS2 resemble disease-active inflammatory cells in releasing cytokines. The research group concluded that ETS2 is a central regulator in macrophages in the context of inflammatory processes such as those that occur in Crohn's disease or ulcerative colitis.
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