Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection

Abstract

Infectious and inflammatory diseases in the intestine remain a serious threat for patients world-wide. Reprogramming of the intestinal epithelium towards a protective effector state is important to manage inflammation and immunity and can be therapeutically targeted. The role of epigenetic regulatory enzymes within these processes is not yet defined. Here, we use a mouse model that has an intestinal-epithelial specific deletion of the histone demethylase Lsd1 (cKO mice), which maintains the epithelium in a fixed reparative state. Challenge of cKO mice with bacteria-induced colitis or a helminth infection model both resulted in increased pathogenesis. Mechanistically, we discovered that LSD1 is important for goblet cell maturation and goblet-cell effector molecules such as RELMß. We propose that this may be in part mediated by directly controlling genes that facilitate cytoskeletal organization, which is important in goblet cell biology. This study therefore identifies intestinal-epithelial epigenetic regulation by LSD1 as a critical element in host protection from infection.

BMP signaling in the intestinal epithelium drives a critical feedback loop to restrain IL-13–driven tuft cell hyperplasia

“…S5C). In accordance with our previous work ( 18 ), confocal staining confirmed that MUC2 was induced by IL-13 (Fig. 2, D and F), and that RELMβ was more strongly induced by IL-22 (Fig.…”

Biosynthesized silver nanoparticles have anticoccidial and jejunum-protective effects in mice infected with Eimeria papillata

“…Goblet cells found in the intestine secrete mucus that acts as an immune-defensive barrier against microbes and parasites that may invade the intestine during food ingestion (Parmar et al 2021 ). Many studies have reported that goblet cells are highly affected by Eimeria infection (Dkhil et al 2013 ; Kim et al 1996 ) In the current study, histological sections of jejuna of E. papillata -infected mice observed on day 5 postinfection showed a reduction in the number of goblet cells (Figs.…”

Interleukin-10 regulates goblet cell numbers through Notch signaling in the developing zebrafish intestine

“…Although we did not find differences in the transcript levels for secretory cell markers in organoids, it is possible that these changes may be visible at a protein level, as observed in zebrafish. In addition, SI organoids do not show elevated numbers of goblet cells under normal sterile growth conditions, thus the addition of inducers of goblet cell differentiation, such as type 2 cytokines or Notch inhibitors 64 would be needed to potentially visualize its regulation by IL-10. Nevertheless, our results from SI organoids match previous findings from single-cell transcriptomic analysis of mouse intestinal organoids, which showed an increased Rgcc expression after IL-10 treatments.…”