Pancreatic cancer is a very aggressive disease with a dismal prognosis. The tumor microenvironment exerts immunosuppressive activities through the secretion of several cytokines, including interleukin (IL)-1. The IL-1/IL-1 receptor (IL-1R) axis is a key regulator in tumor-promoting T helper (Th)2- and Th17-type inflammation. Th2 cells are differentiated by dendritic cells endowed with Th2-polarizing capability by the thymic stromal lymphopoietin (TSLP) that is secreted by IL-1-activated cancer-associated fibroblasts (CAFs). Th17 cells are differentiated in the presence of IL-1 and other IL-1-regulated cytokines. In pancreatic cancer, the use of a recombinant IL-1R antagonist (IL1RA, anakinra, ANK) in in vitro and in vivo models has shown efficacy in targeting the IL-1/IL-1R pathway. In this study, we have developed sphingomyelin nanosystems (SNs) loaded with ANK (ANK-SNs) to compare their ability to inhibit Th2- and Th17-type inflammation with that of the free drug in vitro. We found that ANK-SNs inhibited TSLP and other pro-tumor cytokines released by CAFs at levels similar to ANK. Importantly, inhibition of IL-17 secretion by Th17 cells, but not of interferon-γ, was significantly higher, and at lower concentrations, with ANK-SNs compared to ANK. Collectively, the use of ANK-SNs might be beneficial in reducing the effective dose of the drug and its toxic effects.

Primary focal segmental glomerulosclerosis (FSGS) is a disease of the podocytes and glomerulus, leading to nephrotic syndrome and progressive loss of renal function. One of the most serious aspects is its recurrence of disease in over 30% of patients following allogeneic kidney transplantation, leading to early graft loss. This research investigates the individual genetic predispositions and differences in the immune responses leading to recurrence of FSGS after transplantation. We performed exome sequencing on six patients with recurrent FSGS to identify variants in fifty-one genes and found significant variations in the alpha-2-macroglobulin (A2M). Immunoblotting was used to investigate effects of specific gene variants at the protein level. Further expression analysis identified A2M, exophilin 5 (EXPH5) and plectin (PLEC) as specific proteins linked to podocytes, endothelial cells, and the glomerulus. Subsequent protein array screening revealed the presence of non-HLA-specific antibodies, including TRIM21, after transplantation. Using Metascape for pathway and process enrichment analysis, we focused on the IL-17 signaling and chemotaxis pathways. ELISA measurements showed significantly elevated IL-17 levels in patients with recurrent FSGS (32.30 ± 9.12 pg/mL) compared to individuals with other glomerular diseases (23.16 ± 2.49 pg/mL; p < 0.01) and healthy subjects (22.28 ± 0.94 pg/mL; p < 0.01), with no significant difference in plasma CCL2/MCP-1 levels between groups. This study explores the molecular dynamics underlying recurrence of FSGS after transplantation, offering insights into potential biomarkers and therapeutic targets for the future development of individualized treatments for transplant patients.

This study aimed to determine whether oral fumonisin exposure contributes to the development of psoriasis. Oral administration of fumonisin B1 (FB1, 0.1 mg/kg) or fumonisin B2 (FB2, 0.1 mg/kg) was conducted for 10 days, in addition to the induction of psoriatic symptoms through topical application of 5% imiquimod cream from day 6 to day 10 (5 days) in female BALB/c mice. The results demonstrated that oral administration of FB2 significantly exacerbated psoriatic symptoms, including skin thickness, itching behavior, transepidermal water loss, immune cell infiltration in the dermis, and proinflammatory cytokine production. However, no changes were observed following exposure to FB1. Our results confirm that oral exposure to FB2 adversely affects the pathogenesis of psoriasis by increasing skin thickness and impairing barrier function.

Exposure to heavy metals and lifestyle factors like smoking contribute to the production of free oxygen radicals. This fact, combined with a lowered total antioxidant status, can induce even more damage in the development of ankylosing spondylitis (AS). Despite the fact that some researchers are looking for more genetic factors underlying AS, most studies focus on polymorphisms within the genes encoding the human leukocyte antigen (HLA) system. The biggest challenge is finding the effective treatment of the disease. Genetic factors and the influence of oxidative stress, mineral metabolism disorders, microbiota, and tobacco smoking seem to be of great importance for the development of AS. The data contained in this review constitute valuable information and encourage the initiation and development of research in this area, showing connections between inflammatory disorders leading to the pathogenesis of AS and selected environmental and genetic factors.

Asthma is a heterogeneous disease that can be broadly classified into type 2, which is primarily steroid-sensitive and eosinophilic, and non-type 2, which is primarily steroid-resistant and neutrophilic. While the mechanisms leading to the development of molecular-targeted therapies for type 2 asthma are being elucidated, much remains to be learned about non-type 2 asthma. To investigate the role of oxidative stress in refractory allergic airway inflammation, we compared asthma models generated by immunizing wild-type and nuclear factor erythroid-2-related factor 2 (Nrf2)-deficient mice with the house dust mite antigen. Both asthma models had similar levels of airway inflammation and hyperresponsiveness, but the Nrf2-deficient mice had increased oxidative stress and exacerbated neutrophilic airway inflammation compared with the wild-type mice. Type 2 cytokines and the expression of GATA3, a transcription factor that is important for Th2 cell differentiation, had decreased in Nrf2-deficient mice compared with the wild-type mice, whereas helper T (Th) 17 cytokines and the expression of RORγt, which is important for Th17 cell differentiation, had increased. Furthermore, the neutrophilic airway inflammation caused by Nrf2 deficiency was ameliorated by interleukin (IL)-17 neutralization. We have concluded that the disruption of the Nrf2-mediated antioxidant defense system contributed to the induction of Th17 differentiation and exacerbated allergic neutrophilic airway inflammation.

Psoriasis is a chronic immune-mediated inflammatory cutaneous disease characterized by elevated levels of inflammatory cytokines and adipokine Lipocalin-2 (LCN-2). Recently, natural plant-based products have been studied as new antipsoriatic compounds. We investigate the ability of a leaf extract of the marine plant Posidonia oceanica (POE) to inhibit psoriatic dermatitis in C57BL/6 mice treated with Imiquimod (IMQ). One group of mice was topically treated with IMQ (IMQ mice) for 5 days, and a second group received POE orally before each topical IMQ treatment (IMQ-POE mice). Psoriasis Area Severity Index (PASI) score, thickness, and temperature of the skin area treated with IMQ were measured in both groups. Upon sacrifice, the organs were weighed, and skin biopsies and blood samples were collected. Plasma and lesional skin protein expression of IL-17, IL-23, IFN-γ, IL-2, and TNF-α and plasma LCN-2 concentration were evaluated by ELISA. PASI score, thickness, and temperature of lesional skin were reduced in IMQ-POE mice, as were histological features of psoriatic dermatitis and expression of inflammatory cytokines and LCN-2 levels. This preliminary study aims to propose P. oceanica as a promising naturopathic anti-inflammatory treatment that could be introduced in Complementary Medicine for psoriasis.

UNASSIGNED: Healthcare is essential for asthma control, however, whether family-supported healthcare improves therapeutic effects in childhood asthma remains unclear.
UNASSIGNED: The enrolled patients were randomly divided into control and intervention groups. The pulmonary function was evaluated by forced expiratory volume in 1 s as a percentage of forced vital capacity (FEV1/FVC) and fractional exhaled nitric oxide (FeNO). Asthma control and life quality were assessed via a childhood asthma control test and pediatric asthma quality of life questionnaire. Inflammatory cytokines interleukin-6 (IL-6) and interleukin-17 (IL-17) were determined by enzyme-linked immunosorbent assay.
UNASSIGNED: No significant differences existed in the basic characteristics of asthma children and their parents among two groups. The increase of FEV1/FVC was higher in the intervention group versus the control group (76.47 ± 10.76% vs 69.76 ± 8.88%, p = 0.001 at the time of post-intervention), and the decrease of FeNO was greater in the intervention group (30.43 ± 6.85 bbp vs 35.64 ± 6.62 bbp, p = 0.003 at the time of post-intervention). Family-supported healthcare highly improved asthma control and quality of life in childhood asthma post-treatment. Meanwhile, the inflammatory cytokines IL-17 (118.14 ± 25.79 pg/mL in intervention group vs 142.86 ± 28.68 pg/mL in control group, p = 0.004 at the time of post-intervention) and IL-6 (103.76 ± 23.11 pg/mL in intervention group vs 119.73 ± 22.68 pg/mL in control group, p = 0.009 at the time of post-intervention) significantly decreased by family-supported healthcare intervention. Importantly, acute exacerbation (80.8% in intervention group vs 95.7% in control group, p = 0.030) and rehospitalization cases (88.5% in intervention group vs 100% in control group, p = 0.028) also decreased by family-supported healthcare intervention.
UNASSIGNED: Family-supported healthcare improves pulmonary function and quality of life while alleviates inflammation, acute exacerbation, and rehospitalization in childhood asthma post-routine treatment.

The etiology of Guillain-Barré syndrome (GBS) may be autoimmune. About two-thirds of patients typically experience their first symptoms within 5 days to 3 weeks after common infectious diseases, surgery, or vaccination. Infection is a triggering factor for over 50% of patients. In recent years, a growing number of studies have indicated that some immune checkpoint inhibitors and COVID-19 may also contribute to the occurrence of GBS. However, drugs are considered a rare cause of GBS. The patient in our case was a 70-year-old man who developed GBS after initiating secukinumab for psoriasis. Upon diagnosis suggesting a potential association between secukinumab and the development of GBS, as per the Naranjo adverse drug reaction (ADR) probability scale, we decided to discontinue the drug. Following this intervention, along with the administration of immunoglobulin, the patient exhibited a significant improvement in extremity weakness. The association of GBS with secukinumab treatment, as observed in this case, appears to be uncommon. The underlying mechanisms that may link secukinumab to the development of GBS are not yet fully understood and warrant further scientific inquiry and rigorous investigation. However, we hope that this report can raise greater awareness and vigilance among medical professionals to enhance the safety of patients\' medication.

[This corrects the article DOI: 10.3389/fimmu.2022.857311.].

Axial spondyloarthritis (axSpA) is characterized by type-17 immune-driven joint inflammation, and intestinal inflammation is present in around 70% of patients. In this study, we asked whether axSpA stool contained Th17-associated cytokines and whether this related to systemic Th17 activation. We measured stool cytokine and calprotectin levels by ELISA and found that patients with axSpA have increased stool IL-17A, IL-23, GM-CSF, and calprotectin. We further identified increased levels of circulating IL-17A+ and IL-17F+ T-helper cell lymphocytes in patients with axSpA compared to healthy donors. We finally assessed stool metabolites by unbiased nuclear magnetic resonance spectroscopy and found that multiple stool amino acids were negatively correlated with stool IL-23 concentrations. These data provide evidence of type-17 immunity in the intestinal lumen, and suggest its association with microbial metabolism in the intestine.