Paraduodenal pancreatitis as diagnostic challenge: clinical and morphological features of patients with pancreatic pathology involving the pancreatic groove.

Background: Paraduodenal pancreatitis (PP) is an inflammation involving the groove zone, delimited by the duodenum lumen, bile duct, and the head of the pancreas. This area may also be involved during acute pancreatitis (AP). The differential diagnosis is clinically relevant, since PP generally persists, whereas AP resolves.

Multimodal Profiling of Peripheral Blood Identifies Proliferating Circulating Effector CD4 T Cells as Predictors for Response to Integrin α4β7-Blocking Therapy in Inflammatory Bowel Disease.

Background & Aims: Despite the success of biological therapies in treating inflammatory bowel disease, managing patients remains challenging due to the absence of reliable predictors of therapy response.

Methods: In this study, we prospectively sampled 2 cohorts of patients with inflammatory bowel disease receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry; single-cell RNA sequencing; single-cell B and T cell receptor sequencing (BCR/TCR-seq); serum proteomics; and multiparametric flow cytometry to comprehensively assess vedolizumab-induced immunologic changes in the peripheral blood and their potential associations with treatment response.

Integrin αVß6 - autoantigen and driver of epithelial remodeling in colon and bile ducts in primary sclerosing cholangitis and inflammatory bowel disease.

Objective: Recently, autoantibodies directed against the epithelial adhesion protein integrin αVβ6 have been identified which strongly associate with ulcerative colitis (UC). We aimed to elucidate whether anti-integrin αVβ6 (anti- αVβ6) is present in primary sclerosing cholangitis (PSC), its associated inflammatory bowel disease or other cholestatic liver diseases and their persistence after proctocolectomy.

Design: We detected anti- αVβ6 by an enzyme-linked immunosorbent assay in sera collected at two German tertiary centers, including healthy controls (N=62), UC (N=36), Crohn's disease (CD, N=65), PSC-IBD (78 samples from N=41 patients), PSC without IBD (PSC, 41 samples from N=18 patients), primary biliary cholangitis (PBC, N=24), autoimmune hepatitis (AIH, N=32), secondary sclerosing cholangitis (SSC, N=12) and metabolic dysfunction-associated steatotic liver disease (MASLD, N=24).

Discrepant Phenotyping of Monocytes Based on CX3CR1 and CCR2 Using Fluorescent Reporters and Antibodies.

Monocytes, as well as downstream macrophages and dendritic cells, are essential players in the immune system, fulfilling key roles in homeostasis as well as in inflammatory conditions. Conventionally, driven by studies on reporter models, mouse monocytes are categorized into a classical and a non-classical subset based on their inversely correlated surface expression of Ly6C/CCR2 and CX3CR1. Here, we aimed to challenge this concept by antibody staining and reporter mouse models.

Fiber rich food suppressed airway inflammation, GATA3 + Th2 cells, and FcεRIα+ eosinophils in asthma.

Background: Allergic Asthma is a disease presenting various endotypes and no current therapies act curative but alleviate disease symptoms. Dietary interventions are gaining increasing importance in regulating immune responses. Furthermore, short chain fatty acids (SFCA), as the main products of dietary fiber's fermentation by the gut bacteria, ameliorate the pathogenesis and disease burden of different illnesses including asthma.

Etrolizumab-s fails to control E-Cadherin-dependent co-stimulation of highly activated cytotoxic T cells.

Despite promising preclinical and earlier clinical data, a recent phase III trial on the anti-β7 integrin antibody etrolizumab in Crohn's disease (CD) did not reach its primary endpoint. The mechanisms leading to this outcome are not well understood. Here we characterize the β7 T cell compartment from patients with CD in comparison to cells from individuals without inflammatory bowel disease.

Blocking GPR15 Counteracts Integrin-dependent T Cell Gut Homing in Vivo.

Background And Aims: The G protein coupled receptor GPR15 is expressed on and functionally important for T cells homing to the large intestine. However, the precise mechanisms by which GPR15 controls gut homing have been unclear. Thus, we aimed to elucidate these mechanisms as well as to explore the potential of targeting GPR15 for interfering with T cell recruitment to the colon in inflammatory bowel disease [IBD].

ATP citrate lyase (ACLY)-dependent immunometabolism in mucosal T cells drives experimental colitis in vivo.

Objective: Mucosal T cells play a major role in inflammatory bowel disease (IBD). However, their immunometabolism during intestinal inflammation is poorly understood. Due to its impact on cellular metabolism and proinflammatory immune cell function, we here focus on the enzyme ATP citrate lyase (ACLY) in mucosal T cell immunometabolism and its relevance for IBD.

Long-term outcomes of cyclosporin induction and ustekinumab maintenance combination therapy in patients with steroid-refractory acute severe ulcerative colitis.

Background: Effective management of patients with acute severe ulcerative colitis (ASUC) is a major challenge and there remains a paucity of available maintenance treatment options after efficacious cyclosporin induction therapy.

Objectives: We investigated the long-term effectiveness and safety of cyclosporin and ustekinumab combination therapy in patients with steroid refractory ASUC.

Design: Monocentric, prospective study.

Endoscopic Ultrasound in Pancreatology: Focus on Inflammatory Diseases and Interventions.

Background: Endoscopic ultrasound (EUS) is a main tool in pancreatology for both diagnosis and therapy. It allows minimally invasive differentiation of various diseases, with a minimal degree of inflammation or anatomic variations. EUS also enables interventional direct access to the pancreatic parenchyma and the retroperitoneal space, the pancreatic duct, the pancreatic masses, cysts, vascular structures for diagnostic and therapeutic purposes.

IL-20 controls resolution of experimental colitis by regulating epithelial IFN/STAT2 signalling.

Objective: We sought to investigate the role of interleukin (IL)-20 in IBD and experimental colitis.

Design: Experimental colitis was induced in mice deficient in components of the IL-20 and signal transducer and activator of transcription (STAT)2 signalling pathways. In vivo imaging, high-resolution mini-endoscopy and histology were used to assess intestinal inflammation.

Healing of the epithelial barrier in the ileum is superior to endoscopic and histologic remission for predicting major adverse outcomes in ulcerative colitis.

Background: Achieving endoscopic remission is a key therapeutic goal in patients with ulcerative colitis (UC) that is associated with favorable long-term disease outcomes. Here, we prospectively compared the predictive value of endoscopic and/or histologic remission against ileal barrier healing for predicting long-term disease behavior in a large cohort of UC patients in clinical remission.

Methods: At baseline, UC patients in clinical remission underwent ileocolonoscopy with assessment of ileal barrier function by confocal endomicroscopy.

NLRP3 Inhibition Leads to Impaired Mucosal Fibroblast Function in Patients with Inflammatory Bowel Diseases.

Background And Aims: Inflammatory bowel diseases (IBD) are characterized by mucosal inflammation and sequential fibrosis formation, but the exact role of the hyperactive NLRP3 inflammasome in these processes is unclear. Thus, we studied the expression and function of the NLRP3 inflammasome in the context of inflammation and fibrosis in IBD.

Methods: We analysed intestinal NLRP3 expression in mucosal immune cells and fibroblasts from IBD patients and NLRP3-associated gene expression via single-cell RNA sequencing and microarray analyses.

Adhesion GPCR Gpr126 (Adgrg6) Expression Profiling in Zebrafish, Mouse, and Human Kidney.

Adhesion G protein-coupled receptors (aGPCRs) comprise the second-largest class of GPCRs, the most common target for approved pharmacological therapies. aGPCRs play an important role in development and disease and have recently been associated with the kidney. Several aGPCRs are expressed in the kidney and some aGPCRs are either required for kidney development or their expression level is altered in diseased kidneys.

IL-3 receptor signalling suppresses chronic intestinal inflammation by controlling mechanobiology and tissue egress of regulatory T cells.

IL-3 has been reported to be involved in various inflammatory disorders, but its role in inflammatory bowel disease (IBD) has not been addressed so far. Here, we determined IL-3 expression in samples from patients with IBD and studied the impact of or deficiency on T cell-dependent experimental colitis. We explored the mechanical, cytoskeletal and migratory properties of and T cells using real-time deformability cytometry, atomic force microscopy, scanning electron microscopy, fluorescence recovery after photobleaching and and cell trafficking assays.

Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis.

Background And Aims: Acute severe steroid-refractory ulcerative colitis remains a medically challenging condition with frequent need of surgery. It can be treated with the calcineurin inhibitor cyclosporine A with the need for therapeutic drug monitoring and significant toxicity. Recently, a novel calcineurin inhibitor, voclosporin, has been approved for the treatment of lupus nephritis with no need for therapeutic drug monitoring and an improved long-term safety profile.

Washout appearance of hepatocellular carcinomas using standardized contrast-enhanced ultrasound (CEUS) including an extended late phase observation - Real-world data from the prospective multicentre DEGUM study.

Background: Non-invasive diagnosis of hepatocellular carcinoma (HCC) in contrast-enhanced ultrasound (CEUS) is based on the combination of arterial phase hyperenhancement (APHE) and subsequent late (>60 seconds) and mild contrast washout (WO). Whereas APHE is seen in the majority of HCC, wash-out pattern may vary in onset and intensity. In some HCC lesions, even no washout is seen at all.

Case Report: IBD-like colitis following CAR T cell therapy for diffuse large B cell lymphoma.

Chimeric antigen receptor (CAR) T cell therapy has become a new mainstay in the treatment of several hematologic malignancies, but the spectrum of associated complications is still incompletely defined. Here, we report the case of a 70-year-old female patient treated with tisagenlecleucel for diffuse large B cell lymphoma (DLBCL), who developed chronic diarrhea with characteristics of inflammatory bowel disease (IBD)-like colitis. CAR T cells were substantially enriched in the colon lamina propria and other diagnoses were ruled out.

Differential Effects of Ontamalimab Versus Vedolizumab on Immune Cell Trafficking in Intestinal Inflammation and Inflammatory Bowel Disease.

Background And Aims: The anti-MAdCAM-1 antibody ontamalimab demonstrated efficacy in a phase II trial in ulcerative colitis and results of early terminated phase III trials are pending, but its precise mechanisms of action are still unclear. Thus, we explored the mechanisms of action of ontamalimab and compared it to the anti-α4β7 antibody vedolizumab.

Methods: We studied MAdCAM-1 expression with RNA sequencing and immunohistochemistry.

Manual cell selection in single cell transcriptomics using scSELpy supports the analysis of immune cell subsets.

Introduction: Single cell RNA sequencing plays an increasing and indispensable role in immunological research such as in the field of inflammatory bowel diseases (IBD). Professional pipelines are complex, but tools for the manual selection and further downstream analysis of single cell populations are missing so far.

Methods: We developed a tool called scSELpy, which can easily be integrated into Scanpy-based pipelines, allowing the manual selection of cells on single cell transcriptomic datasets by drawing polygons on various data representations.