Colon mucus segregates the intestinal microbiota from host tissues, but how it organizes to function throughout the colon is unclear. In mice, we found that colon mucus consists of two distinct O-glycosylated entities of Muc2: a major form produced by the proximal colon, which encapsulates the fecal material including the microbiota, and a minor form derived from the distal colon, which adheres to the major form. The microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells. In turn, O-glycans on proximal colon–derived Muc2 modulate the structure and function of the microbiota as well as transcription in the colon mucosa. Our work shows how proximal colon control of mucin production is an important element in the regulation of host-microbiota symbiosis.

The liver has recently been identified as a major organ for destruction of desialylated platelets. However, the underlying mechanism remains unclear. Kupffer cells, which are professional phagocytic cells in the liver, comprise the largest population of resident tissue macrophages in the body. Kupffer cells express a C-type lectin receptor, CLEC4F, that recognizes desialylated glycans with an unclear in vivo role in mediating platelet destruction. In this study, we generated a CLEC4F-deficient mouse model (Clec4f−/−) and found that CLEC4F was specifically expressed by Kupffer cells. Using the Clec4f−/− mice and a newly generated platelet-specific reporter mouse line, we revealed a critical role for CLEC4F on Kupffer cells in mediating destruction of desialylated platelets in the liver in vivo. Platelet clearance experiments and ultrastructural analysis revealed that desialylated platelets were phagocytized predominantly by Kupffer cells in a CLEC4F-dependent manner in mice. Collectively, these findings identify CLEC4F as a Kupffer cell receptor important for the destruction of desialylated platelets induced by bacteria-derived neuraminidases, which provide new insights into the pathogenesis of thrombocytopenia in disease conditions such as sepsis.

Inflammatory bowel disease (IBD) affects 0.3% of the global population, yet the etiology remains poorly understood. Anti-inflammation therapy has shown great success, but only 60% of patients with IBD benefit from it, indicating that new targets are needed. Here, we report the discovery of an intrinsic counter regulatory mechanism in colitis pathogenesis that may be targeted for IBD treatment. In response to microbial invasion, resident Vimentin+ stromal cells, connective tissue cells genetically marked by Twist2, are activated during the propagation phase of the disease, but not during initiation and resolution phases, and become a primary source of prostaglandin E2 (PGE2). PGE2 induction requires a nuclear factor κB–independent, TLR4-p38MAPK-Cox2 pathway activation. Ablation of each of the pathway genes, but not Rela or Tgfb1, in Twist2 cells enhanced M1 macrophage polarization and granulocyte/T helper 1 (TH1)/TH17 infiltration and aggravated colitis development. PGE2 administration ameliorated colitis in mouse models with defective PGE2 production but not in animals with normal PGE2 induction. Analysis of clinical samples and public domain data revealed increased expression of Cox2, the rate-limiting enzyme of PGE2 biosynthesis, in inflamed tissues, and especially in colon Vimentin+Twist2+ stromal cells, in about 60% of patients with active Crohn’s disease or ulcerative colitis. Moreover, Cox2 protein expression was negatively correlated with disease severity, suggesting an involvement of stromal cells in IBD pathogenesis. Thus, the study uncovers an active immune pathway in colitic inflammation that may be targeted to treat patients with IBD with defects in PGE2 production.

Background Apolipoprotein (Apo) may be associated with type 2 diabetes (T2D), however, little is known whether or not serum apolipoproteins are correlated with fasting blood glucose (FBG) and the prevalence of T2D in Chinese populations. In this study, we examined the association of serum ApoA1, ApoB, and the ratio of ApoB/ApoA1 (ApoB/A1 ratio) with T2D and FBG level, and compared apolipoprotein indicators in predicting T2D in Chinese adults. Methods A total of 1027 subjects were enrolled in this cross-sectional study. The association of ApoA1, ApoB, and ApoB/A1 ratio with T2D prevalence was determined using logistic regression models. Multivariate-analysis of covariance (ANCOVA) was performed for comparisons of the mean difference in FBG level. Results We found that ApoB and ApoB/A1 ratio were positively associated with T2D prevalence and FBG, while inverse association was noted between ApoA1 and T2D prevalence as well as FBG. Stratified analyses for sex, age, body mass index (BMI), smoking, and alcohol consumption showed no significant difference for the association of ApoA1, ApoB, and ApoB/A1 ratio with the prevalence of T2D among subgroups (all p-interactions> 0.05). Nonetheless, ApoA1 poorly performed in predicting T2D as it provided an AUC value of 0.310 that was significantly lower than those observed for ApoB (AUC value: 0.631) and ApoB/A1 ratio (AUC value: 0.685). Finally, path analyses indicated that the association between ApoB and T2D was mediated by BMI. Conclusions This study reveals the association of serum ApoA1, ApoB, and ApoB/A1 ratio with T2D and FBG in Chinese adults, suggesting that ApoB and ApoB/A1 ratio may be early indicators for predicting T2D. Prospective investigation in large cohort is needed.