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Immune checkpoint blockade has become standard treatment for many types of cancer. Such therapy is indicated most often in patients with advanced or metastatic disease but has been increasingly used as adjuvant therapy in those with early-stage disease. Adverse events include immune-related organ inflammation resembling autoimmune diseases. We describe a case of severe immune-related gastroenterocolitis in a 4-month-old infant who presented with intractable diarrhea and failure to thrive after in utero exposure to pembrolizumab. Known causes of the symptoms were ruled out, and the diagnosis of pembrolizumab-induced immune-related gastroenterocolitis was supported by the results of histopathological assays, immunophenotyping, and analysis of the level of antibodies against programmed cell death protein 1 (PD-1). The infant’s condition was successfully treated with prednisolone and infliximab. After a pregnant woman with melanoma received pembrolizumab therapy, severe autoimmune enteritis developed in her healthy newborn infant. The condition was treated with prednisolone and infliximab.

The necessary replacement of fish meal with other protein source in diets of commercially important fish has prompted the study of the effect of the inclusion of different vegetable proteins sources on growth performance and on the gastro-intestinal tract. Currently, soybean meal is the primary protein source as a fish meal replacement because of its low price and high availability. Likewise, it is been documented that the ingestion of soybean meal by several fish species, such as salmonids and carp, triggers a type of intestinal inflammation called enteritis. In this paper, we analyzed the effects of the ingestion of soybean meal and two of its components, soy protein and soy saponin, on zebrafish to establish the basis for using zebrafish larvae as a model for fish nutrition. We took advantage of the existence of different transgenic lines, which allowed us to perform in vivo analysis. Our results indicated that larvae that were feed with soybean meal developed a clear intestinal inflammation as early as two day after beginning the diet. Moreover, we determined that is not the soy protein present in the diet but the soy saponin that is primarily responsible for triggering the immune response. These findings support the use of zebrafish screening assays to identify novel ingredients that would to improved current fish diets or would formulate new ones.

A20, encoded by the TNFAIP3 gene, is a protein linked to Crohn’s disease and celiac disease in humans. We now find that mice expressing point mutations in A20’s M1-ubiquitin–binding zinc finger 7 (ZF7) motif spontaneously develop proximal enteritis that requires both luminal microbes and T cells. Cellular and transcriptomic profiling reveals expansion of Th17 cells and exuberant expression of IL-17A and IL-22 in intestinal lamina propria of A20 ZF7 mice. While deletion of IL-17A from A20 ZF7/ZF7 mice exacerbates enteritis, deletion of IL-22 abrogates intestinal epithelial cell hyperproliferation, barrier dysfunction, and alarmin expression. Colonization of adult germ-free mice with microbiota from adult WT specific pathogen–free mice drives duodenal IL-22 expression and duodenitis. A20 ZF7/ZF7 Th17 cells autonomously express more RORγt and IL-22 after differentiation in vitro. ATAC sequencing identified an enhancer region upstream of the Il22 gene, and this enhancer demonstrated increased activating histone acetylation coupled with exaggerated Il22 transcription in A20 ZF7/ZF7 T cells. Acute inhibition of RORγt normalized histone acetylation at this enhancer. Finally, CRISPR/Cas9–mediated ablation of A20 ZF7 in human T cells increases RORγt expression and IL22 transcription. These studies link A20’s M1-ubiquitin binding function with RORγt expression, expansion of Th17 cells, and epigenetic activation of IL-22–driven enteritis.

Necrotic enteritis is an economically important poultry disease caused by the bacterium Clostridium perfringens. There are currently no necrotic enteritis vaccines commercially available for use in broiler birds, the most important target population. Salmonella-vectored vaccines represent a convenient and effective option for controlling this disease. We used a single attenuated Salmonella vaccine strain, engineered to lyse within the host, to deliver up to three C. perfringens antigens. Two of the antigens were toxoids, based on C. perfringens α-toxin and NetB toxin. The third antigen was fructose-1,6-bisphosphate aldolase (Fba), a metabolic enzyme with an unknown role in virulence. Oral immunization with a single Salmonella vaccine strain producing either Fba, α-toxoid and NetB toxoid, or all three antigens, was immunogenic, inducing serum, cellular and mucosal responses against Salmonella and the vectored C. perfringens antigens. All three vaccine strains were partially protective against virulent C. perfringens challenge. The strains delivering Fba only or all three antigens provided the best protection. We also demonstrate that both toxins and Fba are present on the C. perfringens cell surface. The presence of Fba on the cell surface suggests that Fba may function as an adhesin.

Many nutritional and epidemiological studies have shown that high consumption of trans fatty acids can cause several adverse effects on human health, including cardiovascular disease, diabetes, and cancer. In the present study, we investigated the effect of trans fatty acids on innate immunity in the gut by observing mice fed with a diet high in trans fatty acids, which have been reported to cause dysbiosis. We used C57BL6/J mice and fed them with normal diet (ND) or high-fat, high-sucrose diet (HFHSD) or high-trans fatty acid, high-sucrose diet (HTHSD) for 12 weeks. 16S rRNA gene sequencing was performed on the mice stool samples, in addition to flow cytometry, real-time PCR, and lipidomics analysis of the mice serum and liver samples. RAW264.7 cells were used for the studies. Mice fed with HTHSD displayed significantly higher blood glucose levels and advanced fatty liver and intestinal inflammation, as compared to mice fed with HFHSD. Furthermore, compared to mice fed with HFHSD, mice fed with HTHSD displayed a significant elevation in the expression of CD36 in the small intestine, along with a reduction in the expression of IL-22. Furthermore, there was a significant increase in the populations of ILC1s and T-bet-positive ILC3s in the lamina propria in mice fed with HTHSD. Finally, the relative abundance of the family , which belongs to the phylum , was significantly higher in mice fed with HFHSD or HTHSD, than in mice fed with ND; between the HFHSD and HTHSD groups, the abundance was slightly higher in the HTHSD group. This study revealed that compared to saturated fatty acid intake, trans fatty acid intake significantly exacerbated metabolic diseases such as diabetes and fatty liver.

Corn gluten meal (CGM) is an important alternative protein source in aquafeed production. However, in turbot (Scophthalmus maximus), CGM could not be effectively utilized because of its low digestibility, the reason for which is still unclear. The purpose of the present study was to investigate and elucidate the cause for the poor utilization of CGM by turbot from the view of gut health. An 8-week feeding trial was conducted with turbot individuals (initial body weight 11.4 ± 0.2 g), which were fed with one of four isonitrogenous and isolipidic diets formulated to include 0%, 21.2%, 31.8%, and 42.6% CGM to progressively replace 0%, 33%, 50%, and 67% fish meal (FM) protein in a FM-based diet, respectively. The results showed that CGM caused dose-dependent decreases in (1) growth performance, nutrient digestibility, and feed utilization; (2) activities of brush-border membrane enzymes; (3) intestinal antioxidant indices of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase activities, and reduced glutathione level; (4) intestinal immune parameters of acid phosphatase activity, complement 3, complement 4, and IgM concentrations. Dose-dependent increases in the severity of the inflammation, with concomitant alterations on microvilli structure and increasing expression of inflammatory cytokine genes of Il-1β, Il-8, and Tnf-α were observed but without a change in the intracellular junctions and the epithelial permeability established by the plasma diamine oxidase activity and D-lactate level examinations. In conclusion, the present work proved that CGM negatively affected the gut health of turbot by inducing enteritis and by decreasing intestinal immunity and antioxidant capacity, which could be one of the reasons for the reduced utilization of CGM by turbot.

Necrotic enteritis (NE), caused by Clostridium perfringens ( C. perfringens ), presents a challenge to the global broiler industry. Evidence suggests that Toll-like receptor (TLR) ligands can enhance the immune responses in chickens and protect them against infectious diseases. This study investigated the protective effects of TLR21 ligand class B CpG oligonucleotides (ODN) against NE in broiler chickens. On day 21 of age, chickens were injected with 50 or 100 μg CpG intramuscularly, and one group was injected with 50 μg CpG followed by a booster dose on day 22. Subsequently, birds were orally challenged with C. perfringens twice daily for three days, starting on day 22. On day 22, intestinal samples were collected for gene expression analysis. On day 25, all birds were euthanized, intestinal lesions were scored, and tissue samples were collected from the intestine for gene expression analysis, lymphocyte subset determination, and histomorphological analysis. Cecal contents were also collected for microbiome analysis. The results demonstrated that CpG pre-treatment, either at a single dose of 100 μg or two doses of 50 μg per bird, reduced lesion scores compared to the positive control. C. perfringens infection increased crypt depth in both the jejunum and ileum in the positive control group compared to both the CpG-treated group. At 22 days of age, CpG administration at doses of 100 μg per bird enhanced expression of TLR21, interleukin (IL)-2, CXCL8, IL-10, and interferon (IFN)-γ mRNA transcripts in both the jejunum and ileum. Additionally, at 25 days of age, the group pretreated with two doses of 50 μg of CpG per bird showed increased expression of all cytokines in both the jejunum and ileum compared to the control groups. The percentage of intestinal lymphocytes was not affected by CpG pre-treatment. However, CpG pretreatment at doses of 100 μg resulted in a higher abundance of the members of families Lactobacillaceae and Bacteroidaceae , which are crucial for maintaining gut health. In conclusion, our findings suggest that pretreatment of chickens with intramuscular administration of CpG may be effective in maintaining gut health during C. perfringens infection.

Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation, and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines, and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells.

Background Lupus enteritis (LE) is a serious manifestation of systemic lupus erythematosus (SLE), yet optimal treatment strategies remain unclear. This study aimed to compare the efficacy of rituximab (RTX) plus glucocorticoids versus glucocorticoids combined with conventional immunosuppressants in patients with moderate-to-severe LE. Methods We retrospectively analyzed 36 patients with SLE-related intestinal involvement treated at our center between January 2015 and August 2024; sixteen received RTX plus glucocorticoids, and twenty received glucocorticoids with conventional immunosuppressants. Baseline characteristics, clinical features, abdominal CT findings, laboratory parameters (including serum and fecal IgA, IL-6, TNF-α, and IL-10), and disease activity scores (SLEDAI-2 K and BILAG-2004) were assessed. For fecal IgA analysis, age- and sex-matched healthy controls without relevant diseases or recent antibiotic/microbiota-modulating use were included. Treatment response and safety outcomes were compared over 6 months. Results Both patient groups exhibited comparable baseline characteristics. Both treatment strategies led to significant improvements in clinical symptoms and imaging abnormalities—including bowel wall thickening, mesenteric effusion, comb sign, or target sign—with no significant differences observed between the groups. After six months of treatment, the median SLEDAI-2 K score in the rituximab (RTX) group decreased from 15 to 0 ( p  < 0.001), and the BILAG-2004 score decreased from 31.5 to 0 ( p  < 0.001). IL-6 levels in the RTX group also significantly declined from 26.57 ± 7.94 pg/mL to 4.15 ± 2.10 pg/mL ( p  < 0.01), with a greater reduction compared to the control group. Fecal IgA levels were higher in lupus enteritis patients than in healthy controls and decreased in both groups following treatment. Baseline IL-6 correlated with SLEDAI-2 K and BILAG-2004 scores, whereas fecal IgA was elevated in patients with mesenteric effusion but not associated with overall disease activity. At 6 months, remission was achieved in 93.8% of RTX-treated patients and 85% of controls ( p  = 0.418), with comparable safety profiles. Conclusion Both RTX plus glucocorticoids and conventional immunosuppressants plus glucocorticoids are effective in inducing clinical and radiologic remission in LE. RTX may lead to faster improvement in certain serologic and inflammatory biomarkers. Larger studies with longer follow-up and stratification by systemic involvement are warranted to optimize individualized treatment strategies.

The application of sortase-mediated surface display technology on Bacillus subtilis represents a novel approach in protein engineering. We developed and evaluated a recombinant chimeric protein (R-anz) integrating truncated forms of three Clostridium perfringens toxins (CPA, NetB, ZMP) displayed on B. subtilis . Bioinformatics analyses using docking demonstrated that the 3D structure of R-anz chimeric protein has the potential to interact with chicken Toll-like receptor 21 (TLR21). Successful expression of the chimeric antigen was confirmed through SDS-PAGE and Western blotting, revealing a 78 kDa band in lysozyme-treated, xylose-induced samples. Oral immunization of chickens with this live bacterial vaccine significantly elevated IgY antibody levels, as assessed by ELISA. Cytokine profiling demonstrated a robust immune response, with marked upregulation of IFN-γ, IL-4, IL-17, and IL-22. Post-challenge with virulent C. perfringens strains, immunized chickens exhibited significantly reduced intestinal lesion scores, indicating partial protection. This study highlights the dual activation of humoral and cellular immune pathways, evidenced by elevated IgY levels and enhanced cytokine responses, particularly IFN-γ, IL-4, and IL-22. While the results demonstrate the potential of the R-anz chimeric protein to mitigate necrotic enteritis (NE), further research is essential to refine its efficacy, explore commercial feasibility, and address industry-specific challenges. This work paves the way for advancing NE vaccines using innovative sortase-mediated surface display technology, offering a promising strategy for sustainable poultry health management.