An insight into the gut microbiota after Schistosoma japonicum eggs immunization in an experimental ulcerative colitis model.

Schistosome infection and schistosome-derived products have been implicated in the prevention and alleviation of inflammatory bowel disease by manipulating the host immune response, whereas the role of gut microbiota in this protective effect remains poorly understood. In this study, we found that the intraperitoneal immunization with Schistosoma japonicum eggs prior to dextran sulfate sodium (DSS) application significantly ameliorated the symptoms of DSS-induced acute colitis, which was characterized by higher body weight, lower disease activity index score and macroscopic inflammatory scores. We demonstrated that the immunomodulatory effects of S. japonicum eggs were accompanied by an influence on gut microbiota composition, abundance, and diversity, which increased the abundance of genus Turicibacter, family Erysipelotrichaceae, phylum Firmicutes, and decreased the abundance of genus Odoribacter, family Marinifilaceae, order Bacteroidales, class Bacteroidia, phylum Bacteroidota. In addition, Lactobacillus was identified as a biomarker that distinguishes healthy control mice from DSS-induced colitis mice. The present study revealed the importance of the gut microbiota in S. japonicum eggs exerting protective effects in an experimental ulcerative colitis (UC) model, providing an alternative strategy for the discovery of UC prevention and treatment drugs.

Anti-integrin αvß6 antibody in Takayasu arteritis patients with or without ulcerative colitis.

Background: It has been well documented that Takayasu arteritis (TAK) and ulcerative colitis (UC) coexist in the same patients. HLA-B*52 characterizes the co-occurrence, which is one of the common genetic features between these two diseases, indicating shared underlying pathologic mechanisms. Anti-integrin αvß6 antibody (Ab) is present in sera of UC patients in a highly specific manner. We investigated if there were any associations between anti-integrin αvß6 Ab and TAK, considering the risk HLA alleles. Methods: A total of 227 Japanese TAK patients were recruited in the current study and their serum samples were subjected to measurement of anti-integrin αvß6 Ab by ELISA. The clinical information, including the co-occurrence of UC, was collected. The HLA allele carrier status was determined by Luminex or genotype imputation. Results: The information about the presence of UC was available for 165 patients, among which eight (4.84%) patients had UC. Anti-integrin αvß6 antibody was identified in 7 out of 8 TAK subjects with UC (87.5%) while only 5 out of 157 (3.18%) TAK subjects without UC had the antibody (OR 121, p=7.46×10-8). A total of 99 out of 218 (45.4%) patients were HLA-B*52 carriers. There was no significant association between the presence of anti-integrin αvß6 Ab and HLA-B*52 carrier status in those without UC (OR 2.01, 95% CI 0.33-12.4, p = 0.189). Conclusions: The prevalence of anti-integrin αvß6 Ab was high in TAK patients with UC, but not in the absence of concomitant UC. The effect of HLA-B*52 on anti-integrin αvß6 Ab production would be minimal.

[Process in the role of vasoactive intestinal peptide in the treatment of ulcerative colitis by regulating the balance of T follicular helper cells/T follicular regulatory cells].

Ulcerative colitis (UC) is an autoimmune disease based on the persistent damage of colonic mucosal barrier. It has been found that the abnormal expression of follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells is closely related to the occurrence and development of UC. Tfh cells can secrete pro-inflammatory factors and assist B cells to produce antibodies, which can promote the development of UC, while Tfr cells can inhibit the activity of Tfh cells and secrete anti-inflammatory factors. How to regulate the balance between them has become one of the potential therapeutic targets of UC. Vasoactive intestinal peptide (VIP) has preventive and therapeutic effect on UC, and its mechanism is closely related to the regulation of Tfh/Tfr cell balance, which can provide help for the treatment of UC.

MicroRNAs in inflammatory bowel disease: What do we know and what can we expect?

MicroRNAs (miRNAs), small non-coding RNAs composed of 18-24 nucleotides, are potent regulators of gene expression, contributing to the regulation of more than 30% of protein-coding genes. Considering that miRNAs are regulators of inflammatory pathways and the differentiation of intestinal epithelial cells, there is an interest in exploring their importance in inflammatory bowel disease (IBD). IBD is a chronic and multifactorial disease of the gastrointestinal tract; the main forms are Crohn's disease and ulcerative colitis. Several studies have investigated the dysregulated expression of miRNAs in IBD, demonstrating their important roles as regulators and potential biomarkers of this disease. This editorial presents what is known and what is expected regarding miRNAs in IBD. Although the important regulatory roles of miRNAs in IBD are clearly established, biomarkers for IBD that can be applied in clinical practice are lacking, emphasizing the importance of further studies. Discoveries regarding the influence of miRNAs on the inflammatory process and the exploration of their role in gene regulation are expected to provide a basis for the use of miRNAs not only as potent biomarkers in IBD but also as therapeutic targets for the control of inflammatory processes in personalized medicine.

mTOR promotes an inflammatory response through the HIF1 signaling pathway in ulcerative colitis.

The imbalance between T helper cell 17 （Th17）and regulatory T cells (Treg) cells leading to inflammation has an important role in the pathogenesis of ulcerative colitis (UC). Mammalian target of rapamycin (mTOR) can regulate the differentiation of T cells, but the specific pathway leading mTOR to regulate Th17/Treg cells in UC remains unclear. Our aim with this study was to investigate the effects of mTOR overexpression and silencing on the hypoxia inducible factor-1α (HIF-1α) - Th17/Treg signaling pathway. To mimic a human study, we established a colon cancer epithelial cell line (HT-29) co-culture system with human CD4+ T cells, and we treated the cells with TNF-α. We observed the effects of mTOR on the HIF-Th17/Treg signaling pathway to determine whether mTOR is involved in the regulatory mechanism. Under the stimulation of TNF-α, the levels of HIF-1α in CD4+T cells were increased in the HT-29 co-culture with CD4+ T cells, promoting glycolysis, increasing the Th17 proportion, decreasing the Treg proportion, increasing the pro-inflammatory factors levels, and decreasing the anti-inflammatory factors levels. Moreover, after mTOR silencing, the HIF-1α level and cell glycolysis levels decreased, Th17 cell differentiation decreased, the pro-inflammatory factor levels decreased, and the anti-inflammatory factor levels increased. In contrast, mTOR overexpression lead to the opposite results.mTOR promotes inflammation by regulating the HIF signaling pathway during UC, and silencing mTOR may alleviate inflammation. An mTOR inhibitor is a potential therapeutic target for UC treatment.

SDH, a novel diarylheptane compound, alleviates dextran sulfate sodium (DSS)-induced colitis by reducing Th1/Th2/Th17 induction and regulating the gut microbiota in mice.

Ulcerative colitis, a chronic inflammatory condition affecting the rectum and colon to varying degrees, is linked to a dysregulated immune response and the microbiota. Sodium (aS,9R)-3-hydroxy-16,17-dimethoxy-15-oxidotricyclo[12.3.1.12,6]nonadeca-1(18),2,4,6(19),14,16-hexene-9-yl sulfate hydrate (SDH) emerges as a novel diarylheptane compound aimed at treating inflammatory bowel diseases. However, the mechanisms by which SDH modulates these conditions remain largely unknown. In this study, we assessed SDH's impact on the clinical progression of dextran sodium sulfate (DSS)-induced ulcerative colitis. Our results demonstrated that SDH significantly mitigated the symptoms of DSS-induced colitis, reflected in reduced disease activity index scores, alleviation of weight loss, shortening of the colorectum, and reduction in spleen swelling. Notably, SDH decreased the proportion of Th1/Th2/Th17 cells and normalized inflammatory cytokine levels in the colon. Furthermore, SDH treatment modified the gut microbial composition in mice with colitis, notably decreasing Bacteroidetes and Proteobacteria populations while substantially increasing Firmicutes, Actinobacteria, and Patescibacteria. In conclusion, our findings suggest that SDH may protect the colon from DSS-induced colitis through the regulation of Th1/Th2/Th17 cells and gut microbiota, offering novel insights into SDH's therapeutic potential.

The impact of 5-aminosalicylates on the efficacy of mesenchymal stem cell therapy in a murine model of ulcerative colitis.

Inflammatory bowel disease (IBD) is distinguished by persistent immune-mediated inflammation of the gastrointestinal tract. Previous experimental investigations have shown encouraging outcomes for the use of mesenchymal stem cell (MSC)-based therapy in the treatment of IBD. However, as a primary medication for IBD patients, there is limited information regarding the potential interaction between 5-aminosalicylates (5-ASA) and MSCs. In this present study, we employed the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model to examine the influence of a combination of MSCs and 5-ASA on the development of UC. The mice were subjected to weight measurement, DAI scoring, assessment of calprotectin expression, and collection of colons for histological examination. The findings revealed that both 5-ASA and MSCs have demonstrated efficacy in the treatment of UC. However, it is noteworthy that 5-ASA exhibits a quicker onset of action, while MSCs demonstrate more advantageous and enduring therapeutic effects. Additionally, the combination of 5-ASA and MSC treatment shows a less favorable efficacy compared to the MSCs alone group. Moreover, our study conducted in vitro revealed that 5-ASA could promote MSC migration, but it could also inhibit MSC proliferation, induce apoptosis, overexpress inflammatory factors (IL-2, IL-12P70, and TNF-α), and reduce the expression of PD-L1 and PD-L2. Furthermore, a significant decrease in the viability of MSCs within the colon was observed as a result of 5-ASA induction. These findings collectively indicate that the use of 5-ASA has the potential to interfere with the therapeutic efficacy of MSC transplantation for the treatment of IBD.

[Research progress of traditional Chinese medicine intervention for ulcerative colitis based on Notch1 signaling pathway].

Ulcerative colitis(UC) is one of the common gastrointestinal diseases worldwide. In recent years, the incidence of UC has been continuously increasing, seriously threatening the health of people globally. It thus has become an urgent problem that needs to be addressed. There is research evidence that intestinal mucosal barrier dysfunction, including changes in intestinal stem cell secretion lineage, mucosal layer damage, disruption of cell junctions, overactive immune function, and imbalanced gut microbiota, is an important pathogenic factor and molecular basis of UC. The Notch signaling pathway is a highly conserved signaling pathway in eukaryotes during evolution, which transmits signals through cell connections between adjacent cells, affecting a series of processes such as cell proliferation, differentiation, development, migration, and apoptosis. Therefore, the Notch signaling pathway can regulate intestinal stem cells, CD4~+T cells, innate lymphoid cells(ILCs), macrophages(MØ), and intestinal microbiota and thus affect the chemical, physical, immune, and biological mucosal barriers of the intestinal mucosa. Its function is extensive and unique, different from those signaling pathways that mainly focus on anti-inflammatory and antioxidant stress. It can explain the therapeutic effects of traditional Chinese medicine from different perspectives. This article reviewed the role of the Notch1 signaling pathway in the pathogenesis of UC and the relevant literature on the targeted prevention and treatment of UC with traditional Chinese medicine, so as to provide new targets and theoretical support for further research on the effective prevention and treatment of UC.

The immune suppressive functions of macrophages are impaired in patients with ulcerative colitis.

Chronic inflammation is the pathological feature of inflammatory bowel diseases (IBD), but its etiology is unknown. Macrophages are one of the major immune cell fractions in the colon. The objectives of this study are to characterize the immune regulatory functions of macrophages in the colon of patients with ulcerative colitis (UC). UC patients (n = 30) were recruited into this study. Colon lavage fluid (CLF) was collected. Macrophages are isolated from the cellular components of CLF. The immune suppressive functions of macrophages were assessed using immunological approaches. We observed that macrophages occupied about half of the proportions of the cellular components in CLF. Lower amounts of IL10 mRNA and proteins were detected in macrophages of the UC group than the normal control (NC) group. The expression of IL10 in CLF macrophages was positively correlated with the UC-associated cytokines, including tumor necrosis factor-α, interleukin (IL)-1ß, IFN-γ, eosinophil-derived mediators, in CLF. The immune suppressive functions of CLF macrophages in UC patients were impaired. The inducibility of IL10 expression of UC M0 cells was defective as compared with NC M0 cells. Exposure to CpG restored the inducibility of IL10 expression in UC M0 cells, and gain the potential to acquire the immune suppressive functions. To sum up, the immune suppressive functions of UC macrophages are impaired. The inducibility of IL10 expression of M0 cells is impaired, which can be restored by the treatment with CpG.

Stachyose Exerts Anticolitis Efficacy by Re-balancing Treg/Th17 and Activating the Butyrate-Derived PPARγ Signaling Pathway.

Ulcerative colitis (UC) is a complex chronic inflammatory disease closely associated with gut homeostasis dysfunction. The previous studies have shown that stachyose, a functional food additive, has the potential to enhance gut health and alleviate UC symptoms. However, the underlying mechanism of its effects remains unknown. In this study, our findings showed that dietary supplements of stachyose had a significant dose-dependent protective effect on colitis symptoms, regulation of gut microbiota, and restoration of the Treg/Th17 cell balance in dextran sulfate sodium (DSS) induced colitis mice. To further validate these findings, we conducted fecal microbiota transplantation (FMT) to treat DSS-induced colitis in mice. The results showed that microbiota from stachyose-treated mice exhibited a superior therapeutic effect against colitis and effectively regulated the Treg/Th17 cell balance in comparison to the control group. Moreover, both stachyose supplementation and FMT resulted in an increase in butyrate production and the activation of PPARγ. However, this effect was partially attenuated by PPARγ antagonist GW9662. These results suggested that stachyose alleviates UC symptoms by modulating gut microbiota and activating PPARγ. In conclusion, our work offers new insights into the benefical effects of stachyose on UC and its potential role in modulating gut microbiota.

TL1A inhibition for inflammatory bowel disease treatment: From inflammation to fibrosis.

The pivotal role of TL1A in modulating immune pathways crucial for inflammatory bowel disease (IBD) and intestinal fibrosis offers a promising therapeutic target. Phase 2 trials (TUSCANY and ARTEMIS-UC) evaluating an anti-TL1A antibody show progress in expanding IBD therapeutic options. First-in-human data reveal reduced expression of genes associated with extracellular matrix remodeling and fibrosis post-anti-TL1A treatment. Investigational drug TEV-48574, potentially exerting dual antifibrotic and anti-inflammatory effects, is undergoing a phase 2 basket study in both ulcerative colitis (UC) and Crohn disease (CD). Results are eagerly awaited, marking advancements in IBD therapeutics. This critical review comprehensively examines the existing literature, illuminating TL1A and the intricate role of DR3 in IBD, emphasizing the evolving therapeutic landscape and ongoing clinical trials, with potential implications for more effective IBD management.

Exploring the molecular mechanisms and shared gene signatures between celiac disease and ulcerative colitis based on bulk RNA and single-cell sequencing: Experimental verification.

Many immune-mediated diseases have the common genetic basis, as an autoimmune disorder, celiac disease (CeD) primarily affects the small intestine, and is caused by the ingestion of gluten in genetically susceptible individuals. As for ulcerative colitis (UC), which most likely involves a complex interplay between some components of the commensal microbiota and other environmental factors in its origin. These two autoimmune diseases share a specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, ulcerative colitis and celiac disease, are not completely understood. Both are complex diseases with genetics and the environmental factors contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. This study is designed to further clarify the relationship between UC and CeD. The GEO database was used to download gene expression profiles for CeD (GSE112102) and UC (GSE75214). The GSEA KEGG pathway analysis revealed that immune-related pathways were significantly associated with both diseases. Further, we screened 187 shared differentially expressed genes (DEGs) of the two diseases. Gene Ontology (GO) and WikiPathways were carried out to perform the biological process and pathway enrichment analysis. Subsequently, based on the DEGs, the least absolute shrinkage and selection operator (LASSO) analysis was performed to screen for the diagnostic biomarkers of the diseases. Moreover, single-cell RNA-sequencing (RNA-seq) data from five colonic propria with UC showed that REG4 expression was present in Goblet cell, Enteroendocrine cell, and Epithelial. Finally, our work identified REG4 is the shared gene of UC and CeD via external data validation, cellular experiments, and immunohistochemistry. In conclusion, our study elucidated that abnormal immune response could be the common pathogenesis of UC and CeD, and REG4 might be a key potential biomarker and therapeutic target for the comorbidity of these two diseases.

Investigating the concomitance of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides and inflammatory bowel disease (IBD).

OBJECTIVE: To assess relationship between Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and inflammatory bowel disease (IBD). METHODS: This is a retrospective study design. The patients were identified using a preset criteria of patients who have the diagnosis of ANCA associated vasculitis including a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) with overlapping inflammatory bowel disease (Crohn's disease or ulcerative colitis) in the time period from 01/01/2020 to 08/03/2023. Subsequently data from each patient was collected that will include baseline demographics, disease characteristics, disease activity, treatment information, multiorgan involvement, and pathology findings which were then analyzed. RESULTS: 39 patients were identified that met criteria. 20 patients carried a diagnosis of GPA, 6 had MPA and 4 patients had EGPA. 20 patients with GPA had inflammatory bowel disease, 13 with ulcerative colitis and 6 with Crohn's disease while 1 GPA patient had unspecified inflammatory bowel disease. 4 patients with EGPA had inflammatory bowel disease, 2 with ulcerative colitis and 2 with Crohn's disease. 6 patients with MPA had inflammatory bowel disease, 4 with ulcerative colitis and 2 with Crohn's disease. IBD diagnosis preceded the diagnosis of ANCA vasculitis in 77.8 % of the cases. CONCLUSION: Objective observation and deductions from this study raise the concern for a possible pathogenic association of ANCA associated vasculitis and inflammatory bowel disease and more research is needed to identify any causal association or influence of the two systemic disease on each other.

Turtle peptide and its derivative peptide ameliorated DSS-induced ulcerative colitis by inhibiting inflammation and modulating the composition of the gut microbiota.

Ulcerative colitis (UC) is a recurrent intestinal disease with an increasing incidence worldwide that seriously affects the life of patients. Turtle peptide (TP) is a bioactive peptide extracted from turtles that has anti-inflammatory, antioxidant and anti-aging properties. However, studies investigating the effect of TP on the progression of UC are lacking. The aim of this study was to investigate effects and underlying mechanisms of TP and its derivative peptide GPAGPIGPV (GP-9) in alleviating UC in mice. The results showed that 500 mg/kg TP treatment significantly ameliorated colitis symptoms and oxidative stress in UC mice. TP alleviated intestinal barrier damage in UC mice by promoting mucosal repair and increasing the expression of tight junction proteins (ZO1, occludin and claudin-1). TP also modulated the composition of the gut microbiota by increasing the abundance of the beneficial bacteria Anaerotignum, Prevotellaceae_UCG-001, Alistipes, and Lachno-spiraceae_NK4A136_group and decreasing the abundance of the harmful bacteria Prevotella_9 and Parasutterella. Furthermore, we characterized the peptide composition of TP and found that GP-9 ameliorated the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice by inhibiting the TLR4/NF-κB signaling pathway. In conclusion, TP and its derivative peptides ameliorated DSS-induced ulcerative colitis by inhibiting the expression of inflammatory factors and modulating the composition of the intestinal microbiota; this study provides a theoretical basis for the application of TP and its derivative peptides for their anti-inflammatory activity.

Panaxynol improves crypt and mucosal architecture, suppresses colitis-enriched microbes, and alters the immune response to mitigate colitis.

Ulcerative colitis (UC) is an idiopathic inflammatory disease of the large intestine, which impacts millions worldwide. Current interventions aimed at treating UC symptoms can have off-target effects, invoking the need for alternatives that may provide similar benefits with less unintended consequences. This study builds on our initial data, which showed that panaxynol-a novel, potent, bioavailable compound found in American ginseng-can suppress disease severity in murine colitis. Here we explore the underlying mechanisms by which panaxynol improves both chronic and acute murine colitis. Fourteen-week-old C57BL/6 female mice were either given three rounds of dextran sulfate sodium (DSS) in drinking water to induce chronic colitis or one round to induce acute colitis. Vehicle or panaxynol (2.5 mg/kg) was administered via oral gavage three times per week for the study duration. Consistent with our previous findings, panaxynol significantly (P < 0.05) improved the disease activity index and endoscopic scores in both models. Using the acute model to examine potential mechanisms, we show that panaxynol significantly (P < 0.05) reduced DSS-induced crypt distortion, goblet cell loss, and mucus loss in the colon. 16S Sequencing revealed panaxynol altered microbial composition to suppress colitis-enriched genera (i.e., Enterococcus, Eubacterium, and Ruminococcus). In addition, panaxynol significantly (P < 0.05) suppressed macrophages and induced regulatory T-cells in the colonic lamina propria. The beneficial effects of panaxynol on mucosal and crypt architecture, combined with its microbial and immune-mediated effects, provide insight into the mechanisms by which panaxynol suppresses murine colitis. Overall, this data is promising for the use of panaxynol to improve colitis in the clinic.NEW & NOTEWORTHY In the current study, we report that panaxynol ameliorates chemically induced murine colitis by improving colonic crypt and mucosal architecture, suppressing colitis-enriched microbes, reducing macrophages, and promoting the differentiation of regulatory T-cells in the colonic lamina propria. This study suggests that this novel natural compound may serve as a safe and effective treatment option for colitis patients.

Combination Therapy With Guselkumab and Golimumab in Patients With Moderately to Severely Active Ulcerative Colitis: Pharmacokinetics, Immunogenicity and Drug-Drug Interactions.

A proof-of-concept study with the combination of guselkumab and golimumab in patients with ulcerative colitis (UC) has shown that the combination therapy resulted in greater efficacy than the individual monotherapies. The current analysis evaluated the pharmacokinetics (PK) and immunogenicity of guselkumab and golimumab in both the combination therapy and individual monotherapies. Blood samples were collected to evaluate serum concentrations and immunogenicity of guselkumab and golimumab. Population PK (PopPK) models were developed to assess the effects of combination therapy and other potential covariates on the PK of guselkumab and golimumab. The guselkumab PK was comparable between monotherapy and combination therapy, whereas golimumab concentrations were slightly higher with combination therapy. The anti-guselkumab antibody incidence was low with both monotherapy and combination therapy, and guselkumab immunogenicity did not impact the clearance. Conversely, the anti-golimumab antibody incidence with combination therapy was lower than that for monotherapy. PopPK analysis suggested that the slightly higher golimumab concentrations with combination therapy were partially due to lower immunogenicity and thus lower clearance with combination therapy. C-reactive protein (CRP) was also a significant covariate on golimumab clearance. The greater improvement of inflammation with combination therapy, as shown by reductions in CRP, may have also contributed to the higher golimumab concentrations. Combination therapy slightly decreased the clearance of golimumab, but not guselkumab clearance, in patients with UC. Lower immunogenicity and greater improvement of inflammation with combination therapy were potential mechanisms for slightly increased golimumab concentrations with combination therapy as compared with golimumab monotherapy.

Anti-integrin αvß6 autoantibodies are a potential biomarker for ulcerative colitis-like immune checkpoint inhibitor-induced colitis.

BACKGROUND: No specific biomarker for immune checkpoint inhibitor (ICI)-induced colitis has been established. Previously, we identified anti-integrin αvß6 autoantibodies in >90% of patients with ulcerative colitis (UC). Given that a subset of ICI-induced colitis is similar to UC, we aimed to clarify the relationship between such autoantibodies and ICI-induced colitis. METHODS: Serum anti-integrin αvß6 autoantibody levels were compared between 26 patients with ICI-induced colitis and 157 controls. Endoscopic images of ICI-induced colitis were centrally reviewed. Characteristics of anti-integrin αvß6 autoantibodies in the ICI-induced colitis patients were compared with those of UC patients. RESULTS: Anti-integrin αvß6 autoantibodies were found in 8/26 (30.8%) patients with ICI-induced colitis and 3/157 (1.9%) controls (P < 0.001). Patients with anti-integrin αvß6 autoantibodies had significantly more typical UC endoscopic features than those without the autoantibodies (P < 0.001). Anti-integrin αvß6 autoantibodies in ICI-induced colitis patients were associated with grade ≥3 colitis (P = 0.001) and steroid resistance (P = 0.005). Anti-integrin αvß6 autoantibody titers correlated with ICI-induced colitis disease activity. Anti-integrin αvß6 autoantibodies of ICI-induced colitis exhibited similar characteristics to those of UC. CONCLUSIONS: Anti-integrin αvß6 autoantibodies may serve as potential biomarkers for the diagnosis, classification, risk management, and monitoring the disease activity, of ICI-induced colitis.

PTIP Deficiency in B Lymphocytes Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.

BACKGROUND: Immune dysregulation contributes to the development of ulcerative colitis (UC). The research on the inflammatory response of UC is mainly focused on T cells, with less understanding of the role of B cells. Pax transactivation domain-interacting protein (PTIP) is essential for the development of B cell subpopulations and humoral immunity. The purpose of this study was to elucidate the role of PTIP in B cells of mice with dextran sodium sulfate (DSS)-induced colitis. METHODS: The B-cell-specific PTIP knockout (PTIP-/-) mice were established by crossbreeding cluster of differentiation (CD)19cre/cre mice with PTIPflox/flox mice. The UC mice were induced by drinking water supplemented with 3.8% Dextran Sulfate Sodium (DSS) (PTIP-/- + DSS). The histological analysis was performed using hematoxylin and eosin staining. The immune cells were isolated using a fluorescence-activated cell sorter. The serum antibodies (immunoglobulin M (IgM) or immunoglobulin G (IgG)) and tumor necrosis factor (TNF)-α were determined by Enzyme linked immunosorbent assay (ELISA). RESULTS: Interestingly, our findings demonstrate that PTIP deficiency in B cells significantly ameliorates UC. In contrast to PTIP-/- + DSS, the wild type (WT) + DSS group showed a more robust increase in disease activity index (DAI) scores (p < 0.05), a substantially shortened colon (p < 0.001) and a decrease of mucous-producing goblet cells and the complete destruction of crypts. Moreover, PTIP-deficient mice manifested markedly altered neutrophil and T-cell distribution in UC (p < 0.05). Although anti-commensal IgG exacerbates UC, we demonstrated, for the first time, that serum natural IgG does not aggravate the pathology of UC. Furthermore, PTIP regulates UC by controlling B-2 cells independently from T cells. CONCLUSIONS: Transplantation of splenic B-2 cells from PTIP-deficient mice protected recipient NOD/ShiltJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt (NCG) mice from severe UC.

FOXP3 variants are independently associated with transforming growth factor Β1 plasma levels in female patients with inflammatory bowel disease.

OBJECTIVE: The aim of this study was to evaluate the association of -924 G>A (rs2232365) and -3279 C>A (rs3761548) FOXP3 variants with IBD susceptibility, clinical and endoscopic activity, and IL-10 and TGF-ß1 plasma levels. METHOD: The study included 110 IBD female patients, 60 with Ulcerative Colitis (UC) and 50 with Crohn's Disease (CD), and 154 female controls. FOXP3 variants were determined with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Plasma levels of IL-10 and TGF-ß1 were determined using immunofluorimetric assay. RESULTS: AA genotype of rs2232365 and rs3761548 was associated with CD (OR = 3.147, 95% CI 1.015-9.758, p = 0.047) and UC (OR = 3.221, 95% CI 1.050-9.876, p = 0.041) susceptibility, respectively. However, were not associated with TGF-ß1 and IL-10 levels, and endoscopic/clinical activity disease. GAGA haplotype was associated with IBD (OR = 4.003, 95% CI 1.100-14.56, p = 0.035) and UC susceptibility (OR = 6.107, 95% CI 1.609-23.18, p = 0.008). In addition, IBD patients with the GAGA haplotype had lower TGF-ß1 levels (p = 0.041). Moreover, G/C haplotype (dominant model) had a protective effect of 60% in CD susceptibility and lower Endoscopic Severity Index. CONCLUSIONS: These results suggest that FOXP3 variants could exert a role in the Treg, which could be one of the factors involved in the susceptibility and pathogenesis of IBD.