Bandarra et al. Featured in Feb Disease Models & Mechanisms February 4, 2015 The February 2015 edition of Disease Models and Mechanisms will feature a cover image from Daniel Bandarra’s paper “HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals.” The work, a collaboration between the Rocha group and Arno Müller of the Division of Cell and Developmental Biology, investigates how the hypoxia-inducing factor system (HIF) regulates transcription factor NF-κB; which is associated with inflammation. Low oxygen (hypoxia) and inflammation are intimately linked and often present in many human diseases. The HIF system plays an important role in the response to low oxygen and comprises several factors and subunits, including HIF-1α. HIF-α is involved in key cellular processes not only during hypoxia but also in non-hypoxic and inflammatory conditions, such as rheumatoid arthritis and diabetes. It is known that the transcription factor nuclear factor κB (NF-κB; which is associated with inflammation) regulates HIF-1α, but little is known about how the HIF system regulates NF-κB. In this study, the authors use human cell lines and Drosophila melanogaster to investigate how HIF-1α regulates NF-κB activity, and they show that HIF-1α represses NF-κB-dependent gene expression. Their results indicate that HIF-1α is required to restrain the NF-κB response and, thus, it is important to prevent excessive and damaging pro-inflammatory responses during infection and inflammation. Furthermore, this study suggests that targeting HIF-1α in disease might result in undesirable secondary effects, with increased angiogenesis and excessive inflammation. The cover image for Disease Models and Mechanisms from Bandarra et al. shows hydrogen peroxide in the gut of Drosophila melanogaster following infection. The paper is available at http://dmm.biologists.org/content/8/2/169.