Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Intestinal epithelial VDR is important for maintaining cellular and physiological levels of TJ protein Claudin-5 to prevent inflammation and tumorigenesis in the colon. At the molecular level, the CLDN-5 gene is a newly discovered downstream target of the transcriptional factor VDR. Lack of VDR led to a reduction of Claudin-5 and more tumors, whereas enhancing VDR increased Claudin-5 to protect the intestinal epithelial cells from tumorigenesis. Overall, we noted a link between VDR signaling and barrier functions in CRC.
Monocyte-derived macrophages (MDM) drive the inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and they are a major source of eicosanoids in airway inflammation. Here we report that MDM from SARS-CoV-2-infected individuals with mild disease show an inflammatory transcriptional and metabolic imprint that lasts for at least 5 months after SARS-CoV-2 infection. MDM from convalescent SARS-CoV-2-infected individuals showed a downregulation of pro-resolving factors and an increased production of pro-inflammatory eicosanoids, particularly 5-lipoxygenase-derived leukotrienes. Leukotriene synthesis was further enhanced by glucocorticoids and remained elevated at 3–5 months, but had returned to baseline at 12 months post SARS-CoV-2 infection. Stimulation with SARS-CoV-2 spike protein or LPS triggered exaggerated prostanoid-, type I IFN-, and chemokine responses in post COVID-19 MDM. Thus, SARS-CoV-2 infection leaves an inflammatory imprint in the monocyte/ macrophage compartment that drives aberrant macrophage effector functions and eicosanoid metabolism, resulting in long-term immune aberrations in patients recovering from mild COVID-19.
Goblet cells through their production and secretion of mucins play an essential role in protecting the host against luminal insults, and contribute to the mutualism between host and gut microbiota. Loss of epithelial Gpr35 disrupts the goblet cell compartment by reducing their numbers and increasing pyroptosis levels. Dysregulation of goblet cells is correlated with changes in the mucosa-associated bacterial communities. As a result, Gpr35f/fVil+ mice displayed increased susceptibility to C. rodentium-induced colitis. (Adapted from SERVIER MEDICAL ART (CC of license 3.0)).
