Interleukin-10 expands transit-amplifying cells while depleting Lgr5+ stem cells via inhibition of Wnt and notch signaling

Abstract

Background & Aims: Epithelial regeneration is essential for homeostasis and mucosal barrier repair. In infectious and immune-mediated intestinal diseases, interleukin (IL)-10 is thought to enhance these processes. We aimed to de ne the mechanism by which IL-10 played in mucosal healing or injury. Methods: Intestinal stem cells (ISCs) cultures and mice were treated with recombinant mice IL-10 (rmIL-10). The level of cell proliferation, differentiation, death and related signaling pathways for self-renewal of ISCs were measured in vitro and in vivo. Results: It was uncovered that rmIL-10 increased the size and death, but reduced the total number of organoids. In addition, rmIL-10 depleted Lgr5 + ISCs and reduced epithelial proliferation, but enhanced the differentiation of epithelial cells and expanded numbers of transit-amplifying (TA) cells. These changes are related to the decrease of Wnt and Notch signals in vivo and in vitro. Meanwhile, increased expression of Paneth cells and decreased expression of enteroendocrine cells and goblet cells were induced by rmIL-10. Conclusions: IL-10 reduces the survival of Lgr5 + ISCs and proliferation of epithelial cells by inhibiting Notch and Wnt signaling, but promotes enhanced the differentiation of epithelial cells and expanded numbers of TA cells. Therefore, IL-10 acts as an anti-in ammatory factor, but may damage intestinal mucosa repair and maybe a potential target for the treatment of intestinal injury.

Gut Microbial Metabolite Pravastatin Attenuates Intestinal Ischemia/Reperfusion Injury Through Promoting IL-13 Release From Type II Innate Lymphoid Cells via IL−33/ST2 Signaling

“…Then, we investigated whether PA exerts protective effects in organoids against H/R injury in vitro. Intestinal organoids are 3D systems comprising ISCs, Paneth and enteroendocrine cells, and other intestinal cell types (26). However, unlike the protective effect of PA against intestinal I/R injury in vivo, PA did not increase organoid viability and did not reduce LDH release after H/R injury in organoids cultured alone (Figures 2G, H).…”

“…The extraction and culture of small intestinal organoids was performed as previously described (6,25,26). For the establishment of the organoid H/R model, the organoids were placed in a humid, anaerobic environment at 37°C for 12 h and then placed in an aerobic environment containing 5% CO 2 in a 37°C incubator for 4 h (6).…”

Integrated Analysis of Ferroptosis and Immunity-Related Genes Associated with Intestinal Ischemia/Reperfusion Injury

“…The mRNAs were reversed into cDNA by kits from Toyobo, according to the previous study. 20 mRNA quantitative analysis was conducted with qRT-PCR using Toyobo SYBR Green Realtime PCR (Applied Biosystems, Foster City, CA) .18S was served as reference gene, and the fold change relative to the control was computed by the 2 −ΔΔCt method. Table 1 displays the Forward and Reverse primer sequences.…”

Screening and Identification of Key Genes, Pathways, and Drugs Associated with Neuropathic Pain in Dorsal Horn: Evidence from Bioinformatic Analysis

“…18s work as the housekeeping gene. Data of RT-PCR were calculated using the 2-ΔΔCt method, 21 and the forward and reverse primer sequences were exhibited in Table S1 .…”