• CAR T-cells
• Cancer
• Clinical trial
• Cytokines
• Immunotherapy
• Vaccine

• Humans
• Neoplasms/immunology
• Neoplasms/therapy
• Neoplasms/pathology
• Cytokines/immunology
• Cytokines/therapeutic use
• Cancer Vaccines/immunology
• Cancer Vaccines/therapeutic use
• T-Lymphocytes/immunology
• Animals
• Immunotherapy
• Tumor Microenvironment/immunology

• biomarkers
• coronary artery disease
• diagnosis

• Humans
• Biomarkers/blood
• Coronary Artery Disease/diagnosis
• Coronary Artery Disease/blood
• MicroRNAs/blood
• Risk Assessment/methods
• C-Reactive Protein/analysis
• Sensitivity and Specificity

• Con A
• Glycyrrhizin
• IL-25
• renal inflammation
• type 2 macrophages

• Animals
• Mice
• Anti-Inflammatory Agents/pharmacology
• Anti-Inflammatory Agents/therapeutic use
• Disease Models, Animal
• Glycyrrhizic Acid/pharmacology
• Glycyrrhizic Acid/therapeutic use
• Hepatorenal Syndrome/chemically induced
• Hepatorenal Syndrome/drug therapy
• Hepatorenal Syndrome/metabolism
• Inflammation/metabolism
• Interleukin-10/metabolism
• Interleukin-1beta/metabolism
• Interleukins/metabolism
• Kidney/pathology
• Kidney/metabolism
• Macrophages/metabolism
• Macrophages/drug effects
• Mice, Inbred C57BL
• Nephritis/drug therapy
• Nephritis/metabolism
• Nephritis/etiology
• Nephritis/prevention & control
• Signal Transduction/drug effects
• Toll-Like Receptor 2/metabolism
• Toll-Like Receptor 4/metabolism
• Concanavalin A
• Hepatitis
• Chemical and Drug Induced Liver Injury/complications
• Chemical and Drug Induced Liver Injury/metabolism

• Eosinophilic inflammations
• Glucocorticoid receptor
• Otitis media
• Sleep apnea

• Humans
• Adenoids/pathology
• Adenoids/metabolism
• Receptors, Glucocorticoid/metabolism
• Male
• Child
• Female
• Hypertrophy
• Eosinophils/metabolism
• Child, Preschool
• Palatine Tonsil/pathology
• Interleukin-17/metabolism
• Mucous Membrane/pathology
• Mucous Membrane/metabolism
• Interleukin-4/metabolism
• Epithelium/pathology
• Epithelium/metabolism
• Glucocorticoids
• Cytokines/metabolism
• Adolescent

• Airway inflammation
• Asthma
• IL-12
• IL-23
• IL-25
• Macrophage polarization
• Neutrophilia

• Humans
• Animals
• Mice
• Interleukin-12/therapeutic use
• Interleukin-17
• Lipopolysaccharides
• Asthma/drug therapy
• Asthma/metabolism
• Cytokines/metabolism
• Inflammation
• Macrophages, Alveolar/metabolism
• Interleukin-23/therapeutic use

• 82170036 National Natural Science Foundation of China

• Adult
• Humans
• Male
• Female
• Child
• Infant
• Child, Preschool
• Middle Aged
• Aged
• Cohort Studies
• Dermatitis, Atopic/epidemiology
• Dermatitis, Atopic/complications
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/epidemiology
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/epidemiology
• Colitis, Ulcerative/diagnosis
• Crohn Disease/complications
• Crohn Disease/epidemiology
• Crohn Disease/diagnosis
• Risk Factors

• Islet autoantibody
• Seroconversion
• Serum cytokine

• Child
• Humans
• Infant
• Child, Preschool
• Diabetes Mellitus, Type 1
• Cytokines
• Seroconversion
• Autoimmunity
• Autoantibodies
• Islets of Langerhans

• Diabetes South Australia
• 3-SRA-2019-899-M-N Juvenile Diabetes Research Foundation Australia and The Leona M. and Harry B. Helmsley Charitable Trust
• 3-SRA-2020-966-M-N Juvenile Diabetes Research Foundation Australia and The Leona M. and Harry B. Helmsley Charitable Trust
• 3-SRA-2017-417-A-N Juvenile Diabetes Research Foundation Australia International Strategic Research Award scheme
• APP1173945 NHMRC Investigator Fellowship
• APP1136735 NHMRC Practitioner Fellowship
• NHMRC Research Institute Infrastructure Support Scheme
• APP1078106 The National Health and Medical Research Council of Australia
• Victorian State Government Operational Infrastructure Support Scheme

• Autoimmune diseases
• Cancer
• Clinical treatment
• IL-25(IL-17E)
• Inflammation

• 82171771 National Natural Science Foundation of China
• 82271854,81971542 National Natural Science Foundation of China
• 91842304, 82071817 National Natural Science Foundation of China

• EAE
• inflammation
• intestinal permeability
• multiple sclerosis
• oleacein

• IL-25
• Inflammatory bowel disease
• Type-2 immunity

• Humans
• Interleukin-17
• Intestines
• Cytokines
• Inflammatory Bowel Diseases/drug therapy
• Epithelial Cells/metabolism
• Intestinal Mucosa

• tumour immunology
• colorectal cancer

• COVID-19
• Pakistan
• cardiac biomarkers
• interleukins

Interleukin-25 (IL-25), also known as IL-17E, is a recently identified cytokine of the IL-17 family. Numerous studies illustrated that the expression of IL-25 is regulated by multiple pathogens, including parasitic, viral, and bacterial infections. IL-25 has a dual function in infectious diseases. On the one hand, IL-25 activates type 2 immunity via the relevant cytokines, including IL-4, IL-5, and IL-13, which are associated with the development of pathogenic infection-related allergic diseases. On the other hand, IL-25 involves in the recruitment of group 2 innate lymphoid cells (ILC2) to enhanced T helper 2 (Th2) cell differentiation, which are important to the clearance of pathogens. However, the precise roles of IL-25 in infectious diseases remain largely unknown. Thus, the current review will shed light on the pivotal roles of IL-25 in infectious diseases.

• Communicable Diseases
• Humans
• Immunity, Innate
• Interleukin-13
• Interleukin-17/metabolism
• Interleukin-4
• Interleukin-5
• Lymphocytes/metabolism

• National Natural Science Foundation of China

• airways
• children
• gut–lung axis
• immunity
• inflammation
• molecular
• pulmonary function tests

• Child
• Humans
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/diagnosis
• Infliximab/therapeutic use
• Lung
• Mesalamine
• Proline

• intestinal epithelial cells
• intestinal inflammation
• macrophages
• mucosal immunity
• stromal cells

Brucellosis is a common bacterial zoonotic infection, and greater than half a million new cases are diagnosed annually. This study investigates the expression of Th2 and Th17 immunity-related factors (Th2-LCR lncRNA, IL-25, TRAF3IP2, and IL-17RB) in different stages of Brucella infections.

In total, 99 brucellosis patients were divided into three groups (acute = first infection before treatment, relapse = before treatment, and treated = after treatment for 6–8 weeks with doxycycline and rifampin). Thirty-three healthy volunteers represented the control group. Gene expression levels were assessed by quantitative amplification in reference to the 18S rRNA gene and statistically evaluated.

No significant differences in the expression of these genes were observed between the control group and patients after completion of antibiotic treatment. Compared to these two groups, only Th2-LCR lncRNA and TRAF3IP2 were significantly more highly expressed in the acute group. Th2-LCR lncRNA was also significantly elevated in the relapse group. TRAF3IP2 expression was additionally significantly increased in the acute group compared to the relapse group.

IL-25 and IL-17RB failed to differentiate between the infected and noninfected groups. TRAF3IP2 and Th2-LCR lncRNA might be good indicators of brucellosis during the acute phase, but the expression levels varied strongly among patients. To verify the suitability of these factors as an indicator for brucellosis, acute infection or relapse should be investigated in further studies on larger cohorts with well-defined inclusion criteria.

• Brucella melitensis
• adaptive immunity
• arthralgias
• cytokines
• lncRNA
• qPCR

VitD3 may contribute to a successful pregnancy through modulation of immune responses, so VitD3 deficiency may have a role in the immunopathogenesis of unexplained recurrent spontaneous abortion (URSA). However, the mechanisms of immunomodulatory actions of VitD3 in decreasing the risk of recurrent spontaneous abortion have not been understood well.

Objective: The purpose of this research was to investigate the influence of 1,25VitD3 on IL-25 and related cytokines of Th17 cells including IL-17A, IL-6, and IL-23 in peripheral blood mononuclear cells of healthy women as a control group and women with unexplained recurrent spontaneous abortion.

Method: Isolation of peripheral blood mononuclear cells (PBMCs) was performed from peripheral blood of the subjects of the studied groups (20 women with URSA as a case group, and 20 control women). The effects of 1,25VitD3 (50 nM, for 24 h) on the studied parameters were evaluated and were compared to the positive and negative controls in vitro. Flow cytometry analysis was used to determine the percentages of regulatory T cells and Th17 cells. For gene expression measurement and cytokines assay, real-time PCR and ELISA were carried out.

Results: The proportion of Th17 cells in women with URSA was considerably higher than in the control group. IL-25 mRNA and protein levels in cultured PBMCs from women with URSA were lower than the controls. 1,25VitD3 increased IL-25 expressions at both the protein and mRNA levels in PBMCs from women with URSA relative to the control group. Additionally, 1,25VitD3 treatment not only significantly decreased the percentage of Th17 cells frequency but also reduced expressions of IL-6, IL-17A, and IL-23 in PBMCs from women with URSA.

Conclusion: 1,25VitD3 may diminish inflammatory responses cells via downregulation of IL-25 expression. It could be an interesting subject for future researches in the field of the immunopathology of URSA to identify molecular pathways in URSA treatment.

• IL-25
• Th17 cells
• URSA
• VitD3
• inflammation

Type 2 immune responses commonly emerge during allergic reactions or infections with helminth parasites. Most of the cytokines associated with type 2 immune responses are IL-4, IL-5, and IL13, which are mainly produced by T helper 2 cells (T_H2), eosinophils, basophils, mast cells, and group 2 innate lymphoid cells (ILC2s). Over the course of evolution, humans have developed type 2 immune responses to fight infections and to protect tissues from the potential collateral damage caused by inflammation. For example, worm parasites induce potent type 2 immune responses, which are needed to simultaneously clear the pathogen and to promote tissue repair following injury. Due to the strong type 2 immune responses induced by helminths, which can promote tissue repair in the damaged epithelium, their use has been suggested as a possible treatment for inflammatory bowel disease (IBD); however, the role of type 2 immune responses in the initiation and progression of IBD is not fully understood. In this review, we discuss the molecular and cellular mechanisms that regulate type 2 immune responses during intestinal homeostasis, and we briefly discuss the scarce evidence linking type 2 immune responses with the aetiology of IBD.

• ILC2
• TH2
• inflammatory bowel disease
• mucosal immunology
• type 2 immunity

• Cancer
• IL-17E
• IL-25
• biomarker
• cytokine

• Animals
• Antineoplastic Agents/therapeutic use
• Apoptosis/physiology
• Benzofurans/therapeutic use
• Bile
• Biomarkers, Tumor/physiology
• Breast Neoplasms/metabolism
• Carcinoma, Hepatocellular/metabolism
• Cell Cycle/physiology
• Cell Proliferation/drug effects
• Disease Progression
• Female
• Humans
• Immunity, Cellular
• Interleukin-17/antagonists & inhibitors
• Interleukin-17/metabolism
• Interleukin-17/physiology
• Liver Neoplasms/metabolism
• Male
• Mice
• Neoplasms/etiology
• Neoplasms/immunology
• Neoplasms/mortality
• Neoplasms/therapy
• Prognosis
• Prostatic Neoplasms/metabolism
• Receptors, Interleukin-17/metabolism
• Receptors, Interleukin-17/physiology
• Signal Transduction/physiology
• Tissue Extracts/therapeutic use
• Tumor Microenvironment/immunology

• IL-25
• IL-25 signal transduction
• rheumatoid arthritis
• systemic erythematosus lupus
• type 2 inflammation

Trauma elicits a complex inflammatory response that, among multiple presenting factors, is greatly impacted by the magnitude of injury severity. Herein, we compared the changes in circulating levels of mediators with known proinflammatory roles to those with known protective/reparative actions as a function of injury severity in injured humans.

Clinical and biobank data were obtained from 472 (trauma database-1 (TD-1), University of Pittsburgh) and 89 (trauma database-2 (TD-2), Indiana University) trauma patients admitted to the intensive care unit (ICU) and who survived to discharge. Injury severity was estimated based on the Injury Severity Score (ISS), and this was used as both a continuous variable and for the purpose of grouping patients into severity-based cohorts. Samples within the first 24 hours were obtained from all patients and then daily up to day 7 postinjury in TD-1. Sixteen cytokines were assayed using Luminex and were analyzed using two-way analysis of variance (p<0.05).

Patients with higher ISSs had longer ICU and hospital stays, days on mechanical ventilation and higher rates of nosocomial infection when compared with the mild and moderate groups. Time course analysis and correlations with ISS showed that 11 inflammatory mediators correlated positively with injury severity, consistent with previous reports. However, five mediators (interleukin (IL)-9, IL-21, IL-22, IL-23 and IL-17E/25) were suppressed in patients with high ISS and inversely correlated with ISS.

These findings suggest that severe injury is associated with a suppression of a subset of cytokines known to be involved in tissue protection and regeneration (IL-9, IL-22 and IL-17E/25) and lymphocyte differentiation (IL-21 and IL-23), which in turn correlates with adverse clinical outcomes. Thus, patterns of proinflammatory versus protective/reparative mediators diverge with increasing ISS.

• accidents
• cytokines
• inflammation
• intensive care units

• Crohn disease
• IL-17E
• IL-25
• asthma
• atopic dermatitis
• chronic rhinosinusitis
• contact dermatitis
• epithelial cells
• idiopathic pulmonary fibrosis
• inflammatory bowel disease
• keratinocytes
• psoriasis
• tuft cells
• ulcerative colitis

• Animals
• Epithelial Cells/immunology
• Humans
• Immunity, Innate/immunology
• Inflammation/immunology
• Interleukin-17/immunology
• Signal Transduction/immunology

• IL-17A
• IL-17E
• periodontal disease
• periodontal treatment/therapy
• smoking
• total anti-oxidant capacity
• total oxidative stress

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease affecting the CNS. Recent studies have indicated that intestinal alterations play key pathogenic roles in the development of autoimmune diseases, including MS. The triterpene oleanolic acid (OA), due to its anti-inflammatory properties, has shown to beneficially influence the severity of the experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We herein investigate EAE-associated gut intestinal dysfunction and the effect of OA treatment.

Mice with MOG_35–55-induced EAE were treated with OA or vehicle from immunization day and were daily analyzed for clinical deficit. We performed molecular and histological analysis in serum and intestinal tissues to measure oxidative and inflammatory responses. We used Caco-2 and HT29-MTX-E12 cells to elucidate OA in vitro effects.

We found that OA protected from EAE-induced changes in intestinal permeability and preserved the mucin-containing goblet cells along the intestinal tract.

Serum levels of the markers for intestinal barrier damage iFABP and monocyte activation sCD14 were consistently and significantly reduced in OA-treated EAE mice. Beneficial OA effects also included a decrease of pro-inflammatory mediators both in serum and colonic tissue of treated-EAE mice. Moreover, the levels of some immunoregulatory cytokines, the neurotrophic factor GDNF, and the gastrointestinal hormone motilin were preserved in OA-treated EAE mice. Regarding oxidative stress, OA treatment prevented lipid peroxidation and superoxide anion accumulation in intestinal tissue, while inducing the expression of the ROS scavenger Sestrin-3. Furthermore, short-chain fatty acids (SCFA) quantification in the cecal content showed that OA reduced the high iso-valeric acid concentrations detected in EAE-mice. Lastly, using in vitro cell models which mimic the intestinal epithelium, we verified that OA protected against intestinal barrier dysfunction induced by injurious agents produced in both EAE and MS.

These findings reveal that OA ameliorates the gut dysfunction found in EAE mice. OA normalizes the levels of gut mucosal dysfunction markers, as well as the pro- and anti-inflammatory immune bias during EAE, thus reinforcing the idea that OA is a beneficial compound for treating EAE and suggesting that OA may be an interesting candidate to be explored for the treatment of human MS.

The online version contains supplementary material available at 10.1186/s12974-020-02042-6.

• Cytokines
• EAE
• Immune markers
• Inflammation
• Intestinal dysfunction
• Mucins
• Multiple sclerosis
• Oleanolic acid
• Oxidative stress
• Triterpenes

• Cytokines
• Periodontal debridement
• Periodontitis
• Saliva
• Serum

• Colitis
• Crohn’s disease
• Fibrosis
• IBD
• IL-17
• Inflammatory bowel disease
• Intestinal fibrosis
• Th17

• CX3CR1
• IL-25
• dual-functionalized mesenchymal stem cells
• inflammatory bowel disease

IL-25, a member of the IL-17 family of cytokines, is known to enhance type 2 immune responses, but suppress type 3 (IL-17A)-mediated immune responses. Mice deficient in IL-1 receptor antagonist (Il1rn^−/− mice) have excessive IL-1 signaling, resulting in spontaneous development of IL-1–, TNF– and IL-17A–dependent aortitis. We found that expression of II25 mRNA was increased in the aortae of Il1rn^−/− mice, suggesting that IL-25 may suppress development of IL-1–, TNF– and IL-17A–dependent aortitis in Il1rn^−/− mice by inhibiting type 3-mediated immune responses. However, we unexpectedly found that Il25^−/−Il1rn^−/− mice showed attenuated development of aortitis, accompanied by reduced accumulation of inflammatory cells such as dendritic cells, macrophages and neutrophils and reduced mRNA expression of Il17a and Tnfa—but not Il4 or Il13—in local lesions compared with Il1rn^−/− mice. Tissue–, but not immune cell–, derived IL-25 was crucial for development of aortitis. IL-25 enhanced IL-1β and TNF production by IL-25 receptor–expressing dendritic cells and macrophages, respectively, at inflammatory sites of aortae of Il1rn^−/− mice, contributing to exacerbation of development of IL-1–, TNF– and IL-17A–dependent aortitis in those mice. Our findings suggest that neutralization of IL-25 may be a potential therapeutic target for aortitis.

• Gastritis
• Helicobacter pylori
• Immunity
• Regulatory T cell
• Vaccine

• Animals
• Bacterial Vaccines/immunology
• Gastritis/microbiology
• Gastritis/prevention & control
• Helicobacter Infections/immunology
• Helicobacter Infections/prevention & control
• Helicobacter pylori/immunology
• Humans

Myeloid derived suppressor cells (MDSC) in the liver microenvironment protects against the inflammation-induced liver injury in fulminant hepatitis (FH). However, the molecular mechanism through which MDSC is recruited into the inflamed liver remain elusive. Here we identified a protein kinase Tpl2 as a critical mediator of MDSC recruitment into liver during the pathogenesis of Propionibacterium acnes/LPS-induced FH. Loss of Tpl2 dramatically suppressed MDSC mobilization into liver, leading to exaggerated local inflammation and increased FH-induced mortality. Mechanistically, although the protective effect of Tpl2 for FH-induced mortality was dependent on the presence of MDSC, Tpl2 neither directly targeted myeloid cells nor T cells to regulate FH pathogenesis, but functioned in hepatocytes to mediate the induction of MDSC-attracting chemokine CXCL1 and CXCL2 through modulating IL-25 (also known as IL-17E) signaling. As a consequence, increased MDSC in the inflamed liver specifically restrained the local proliferation of infiltrated pathogenic CD4⁺ T cells, and thus protected against the inflammation-induced acute liver failure. Together, our findings established Tpl2 as a critical mediator of MDSC recruitment and highlighted the therapeutic potential of Tpl2 for the treatment of FH.

• IL-25
• TPL2
• chemokine
• hepatitis
• myeloid-derive suppressor cells (MDSCs)

Dendritic cells (DCs) are the professional antigen-presenting cells that recognize and present antigens to naïve T cells to induce antigen-specific adaptive immunity. Among the T-cell subsets, T helper type 2 (Th2) cells produce the humoral immune responses required for protection against helminthic disease by activating B cells. DCs induce a Th2 immune response at a certain immune environment. Basophil, eosinophil, mast cells, and type 2 innate lymphoid cells also induce Th2 immunity. However, in the case of DCs, controversy remains regarding which subsets of DCs induce Th2 immunity, which genes in DCs are directly or indirectly involved in inducing Th2 immunity, and the detailed mechanisms underlying induction, regulation, or maintenance of the DC-mediated Th2 immunity against allergic environments and parasite infection. A recent study has shown that a genetic defect in DCs causes an enhanced Th2 immunity leading to severe atopic dermatitis. We summarize the Th2 immune-inducing DC subsets, the genetic and environmental factors involved in DC-mediated Th2 immunity, and current therapeutic approaches for Th2-mediated immune disorders. This review is to provide an improved understanding of DC-mediated Th2 immunity and Th1/Th2 immune balancing, leading to control over their adverse consequences.

• Th2 disorders
• Th2 immunity
• dendritic cells
• environmental factors
• genetic factors
• therapeutic approaches

• Animals
• Dendritic Cells/immunology
• Humans
• Immune System Diseases/immunology
• Immune System Diseases/therapy
• Immunotherapy/methods
• Th2 Cells/immunology

• HI16C1074 Korea Health Industry Development Institute

Interleukin (IL)-17A has a direct contribution in early induction and late chronic stages of various inflammatory diseases. In vitro and in vivo experiments have first characterized its local effects on different cell types and then its systemic effects. For instance, IL-17 axis is now identified as a key driver of psoriasis through its effects on keratinocytes. Similar observations apply for rheumatoid arthritis (RA) where IL-17A triggers changes in the synovium that lead to synovitis and maintain local inflammation. These results have prompted the development of biologics to target this cytokine. However, while convincing studies are reported on the efficacy of IL-17 inhibitors in psoriasis, there are conflicting results in RA. Patient heterogeneity but also the involvement of mediators that regulate IL-17 function may explain these results. Therefore, new tools and concepts are required to identify patients that could benefit from these IL-17 targeted therapies in RA and the development of predictive biomarkers of response has started with the emergence of various bioassays. Current strategies are also focusing on synovial biopsies that may be used to stratify patients. From local to systemic levels, new approaches are developing and move the field of RA management into the era of precision medicine.

• interleukin-17
• interleukin-17 inhibition
• precision medicine
• rheumatoid arthritis
• synovitis

• Inflammation
• Microbiota
• Mouse Models Colon Carcinogenesis

• Adaptive Immunity/immunology
• Animals
• Colorectal Neoplasms/immunology
• Colorectal Neoplasms/microbiology
• Gastrointestinal Microbiome/immunology
• Humans
• Interleukin-17/immunology
• Intestinal Mucosa/immunology
• Intestinal Mucosa/microbiology
• Mice
• Th1 Cells/immunology
• Th17 Cells/immunology

• R01 CA179440 NCI NIH HHS
• R01 GM111682 NIGMS NIH HHS
• P30 DK089502 NIDDK NIH HHS
• R01 CA203891 NCI NIH HHS
• R01 CA196845 NCI NIH HHS

• IL-17 family
• IL-17A
• IL-17E
• IL-25
• Th17 cells
• comorbidities
• interleukin
• psoriasis

• Ginsenoside Rd
• Inflammation
• NLRP3 Inflammasome
• P62
• Ulcerative colitis

• IL-25
• Oxidized LDL
• Th17

The expression of heat shock protein gp96 is strongly correlated with the degree of tissue inflammation in ulcerative colitis and Crohn’s disease, thereby leading us to the hypothesis that inhibition of expression via gp96-II peptide prevents intestinal inflammation.

We employed daily injections of gp96-II peptide in two murine models of intestinal inflammation, the first resulting from five daily injections of IL-12/IL-18, the second via a single intrarectal application of TNBS (2,4,6-trinitrobenzenesulfonic acid). We also assessed the effectiveness of gp96-II peptide in murine and human primary cell culture.

In the IL-12/IL-18 model, all gp96-II peptide-treated animals survived until day 5, whereas 80% of placebo-injected animals died. gp96-II peptide reduced IL-12/IL-18-induced plasma IFNγ by 89%, IL-1β by 63%, IL-6 by 43% and tumor necrosis factor (TNF) by 70% compared to controls. The clinical assessment Disease Activity Index of intestinal inflammation severity was found to be significantly lower in the gp96-II-treated animals when compared to vehicle-injected mice. gp96-II peptide treatment in the TNBS model limited weight loss to 5% on day 7 compared with prednisolone treatment, whereas placebo-treated animals suffered a 20% weight loss. Histological disease severity was reduced equally by prednisolone (by 40%) and gp96-II peptide (35%). Mice treated with either gp96-II peptide or prednisolone exhibited improved endoscopic scores compared with vehicle-treated control mice: vascularity, fibrin, granularity, and translucency scores were reduced by up to 49% by prednisolone and by up to 30% by gp96-II peptide. In vitro, gp96-II peptide reduced TLR2-, TLR4- and IL-12/IL-18-induced cytokine expression in murine splenocytes, with declines in constitutive IL-6 (54%), lipopolysaccharide-induced TNF (48%), IL-6 (81%) and in Staphylococcus epidermidis-induced TNF (67%) and IL-6 (81%), as well as IL-12/IL-18-induced IFNγ (75%). gp96-II peptide reduced IL–1β, IL-6, TNF and GM-CSF in human peripheral blood mononuclear cells to a similar degree without affecting cell viability, whereas RANTES, IL-25 and MIF were twofold to threefold increased.

gp96-II peptide protects against murine intestinal inflammation by regulating inflammation in vivo and in vitro, pointing to its promise as a novel treatment for inflammatory bowel disease.

• Gp96
• anti-inflammatory agent
• biologics
• cytokines and inflammation
• immunemodulatory
• inflammatory bowel disease
• intestinal inflammation
• therapeutics

• gastric cancer
• interleukin-25
• macrophages
• transforming growth factor-β1

Interleukin (IL)-25, which is a member of the IL-17 family of cytokines, induces production of such Th2 cytokines as IL-4, IL-5, IL-9 and/or IL-13 by various types of cells, including Th2 cells, Th9 cells and group 2 innate lymphoid cells (ILC2). On the other hand, IL-25 can suppress Th1- and Th17-associated immune responses by enhancing Th2-type immune responses. Supporting this, IL-25 is known to suppress development of experimental autoimmune encephalitis, which is an IL-17-mediated autoimmune disease in mice. However, the role of IL-25 in development of IL-17-mediated arthritis is not fully understood. Therefore, we investigated this using IL-1 receptor antagonist-deficient (IL-1Ra^-/-) mice, which spontaneously develop IL-17-dependent arthritis. However, development of spontaneous arthritis (incidence rate, disease severity, proliferation of synovial cells, infiltration of PMNs, and bone erosion in joints) and differentiation of Th17 cells in draining lymph nodes in IL-25^-/- IL-1Ra^-/- mice were similar to in control IL-25^+/+ IL-1Ra^-/- mice. These observations indicate that IL-25 does not exert any inhibitory and/or pathogenic effect on development of IL-17-mediated spontaneous arthritis in IL-1Ra^-/- mice.

•

IL-25 is known to inhibit Th17 cell differentiation.

• Heligmosomoides polygyrus
• Nippostrongylus brasiliensis
• Trichinella spiralis
• Dendritic cell
• T lymphocyte
• Th2 cell
• Trichuris spp.