Intestinal epithelial pH-sensing receptor GPR65 maintains mucosal homeostasis via regulating antimicrobial defense and restrains gut inflammation in inflammatory bowel disease.

Intestinal epithelial cell (IEC) regulation of barrier function and mucosal homeostasis enables the establishment of a harmonious gut microenvironment. However, host-derived regulatory networks that modulate intestinal antimicrobial defenses have not been fully defined. Herein we generated mice with IEC-specific deletion of () and investigated the role of epithelial GPR65 using DSS- and -induced murine colitis models.

Integrative multi-omics deciphers the spatial characteristics of host-gut microbiota interactions in Crohn's disease.

Dysregulated host-microbial interactions play critical roles in initiation and perpetuation of gut inflammation in Crohn's disease (CD). However, the spatial distribution and interaction network across the intestine and its accessory tissues are still elusive. Here, we profile the host proteins and tissue microbes in 540 samples from the intestinal mucosa, submucosa-muscularis-serosa, mesenteric adipose tissues, mesentery, and mesenteric lymph nodes of 30 CD patients and spatially decipher the host-microbial interactions.

MCPIP1 restrains mucosal inflammation by orchestrating the intestinal monocyte to macrophage maturation via an ATF3-AP1S2 axis.

Objective: Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) is highly expressed in inflamed mucosa of inflammatory bowel disease (IBD) and negatively regulates immune response, while the underlying mechanisms regulating mucosal macrophage functions remain unknown. Here, we investigated the roles of MCPIP1 in modulating the differentiation and functions of intestinal macrophages in the pathogenesis of IBD.

Design: ScRNA-seq was used to cluster the monocyte/macrophage lineage from macrophage-specific -deficient ( ) mice and littermates.

Dysregulation of CD177 neutrophils on intraepithelial lymphocytes exacerbates gut inflammation via decreasing microbiota-derived DMF.

Neutrophils synergize with intestinal resident intraepithelial lymphocytes (IELs) to serve as the first-line defense and maintain intestinal homeostasis. However, the underlying mechanisms whereby neutrophils regulate IELs to inhibit intestinal inflammation are still not completely understood. Here, we found that depletion of neutrophils (especially CD177 subset) caused expansion of colitogenic TCRγδCD8αα IELs, increased intestinal inflammation, and dysbiosis after dextran sulfate sodium exposure or infection in mice.

MCPIP-1-Mediated Immunosuppression of Neutrophils Exacerbates Acute Bacterial Peritonitis and Liver Injury.

Monocyte chemotactic protein-1-induced protein-1 (MCPIP-1) is highly expressed in activated immune cells and negatively regulates immune responses, while the mechanisms underlying the immunoregulation of neutrophils in acute bacterial infection and liver injury remain elusive. Here, we examined the role of MCPIP-1 in regulating neutrophil functions during acute bacterial peritonitis and liver injury. Mice with myeloid cell-specific overexpression (McpipMye-tg) or knockout (McpipΔMye) of MCPIP-1 were generated.

ETS-1 facilitates Th1 cell-mediated mucosal inflammation in inflammatory bowel diseases through upregulating CIRBP.

Background & Aims: As a susceptibility gene for human inflammatory bowel diseases (IBD), how avian erythroblastosis virus E26 oncogene homolog-1 (ETS-1) modulates intestinal mucosal immune response remains unclear. Here we studied the potential roles of ETS-1 in the pathogenesis of IBD.

Methods: ETS-1 expression was examined in IBD patients.

GPR65 promotes intestinal mucosal Th1 and Th17 cell differentiation and gut inflammation through downregulating NUAK2.

G protein-coupled receptor 65 (GPR65), a susceptibility gene for inflammatory bowel diseases (IBD), has been identified to promote Th17 cell pathogenicity and induce T cell apoptosis. However, the potential role of GPR65 in modulating CD4 T cell immune responses in the pathogenesis of IBD stills not entirely understood. Here, we displayed that GPR65 expression was increased in inflamed intestinal mucosa of IBD patients and positively associated with disease activity.

Natural Herbal Remedy Wumei Decoction Ameliorates Intestinal Mucosal Inflammation by Inhibiting Th1/Th17 Cell Differentiation and Maintaining Microbial Homeostasis.

Background: Evidence has shown that the traditional Chinese herbal medicine Wumei decoction (WMD) has a protective effect on ulcerative colitis. Here, we studied the anti-inflammatory effects and potential mechanisms of WMD on chronic colitis in mice.

Methods: A dextran sulfate sodium (DSS)-induced chronic colitis model and CD45RBhighCD4+ T cell transfer model were established in mice.

Long-term exclusive enteral nutrition remodels the gut microbiota and alleviates TNBS-induced colitis in mice.

: Exclusive enteral nutrition (EEN) provides an effective strategy for the induction of clinical remission in pediatric Crohn's disease. However, the feasibility of long-term EEN in the management of disease and the underlying mechanism whereby long-term EEN prevents intestinal inflammation are still not fully understood. : Paired male and female adult wild-type (WT) mice were mated to breed littermates, and these pups were then weaned at 3 weeks of age and randomly allocated into regular diet (RT) feeding group and EEN feeding group (Peptisorb; NUTRICIA), respectively.

Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease.

Host-microbial cross-talk plays a crucial role in maintenance of gut homeostasis. However, how microbiota-derived metabolites, e.g.

Monocyte Chemotactic Protein 1-Induced Protein 1 Is Highly Expressed in Inflammatory Bowel Disease and Negatively Regulates Neutrophil Activities.

Monocyte chemotactic protein 1-induced protein 1 (MCPIP-1) is highly expressed in activated immune cells and plays an important role in negatively regulating immune responses. However, its role in regulating neutrophil functions in the pathogenesis of inflammatory bowel disease (IBD) is still unclear. Here, we found that MCPIP-1 was markedly increased at both the transcriptional and translational levels in inflamed mucosa of IBD patients compared with healthy controls, which was mainly expressed in neutrophils.

Anti-TNF- Monoclonal Antibody Therapy Improves Anemia through Downregulating Hepatocyte Hepcidin Expression in Inflammatory Bowel Disease.

Anemia is one of the most common complications in patients with inflammatory bowel disease (IBD). Hepcidin as a key regulator of iron metabolism is pivotal in mediating the occurrence of anemia of chronic disease. Herein, we analyzed the levels of hepcidin in sera from IBD patients by enzyme-linked immunosorbent assay and investigated its potential role in regulating the anemia in IBD.

Survivin Impairs the Apoptotic Machinery in CD4+ T Cells of Patients with Ulcerative Colitis.

Background: The increase in CD4+ T cell infiltration and overproduction of CD4+ T cell-associated cytokines have been observed in the inflamed colon mucosa of patients with ulcerative colitis (UC); the underlying mechanisms are not fully understood. Survivin plays a critical role in the interference with apoptotic machinery. This study aims to elucidate the role of survivin in the interference with the apoptotic machinery in CD4+ T cells of UC patients.