T helper 17 (Th17) cells regulate inflammatory processes and are implicated in pathogenesis of proliferative diabetic retinopathy (PDR) through modulation of interleukin-17 (IL-17). IL-35, anti-inflammatory factor, negatively mediates IL-17 expression and Th17 differentiation. In this study, the role of IL-35 in PDR was assessed. The results showed that IL-35 was down-regulated, while IL-17 was up-regulated, in peripheral blood mononuclear cells (PBMCs) of PDR patients. In addition, immunofluorescence analysis indicated that frequency of Th17 cells was enhanced in the PBMCs of PDR patients. However, incubation with IL-35 reduced the Th17 cell frequency and decreased the level of IL-17 in CD4+ T lymphocytes. Moreover, the levels of transcription factors essential for Th17 differentiation, ROR α (retinoid-related orphan receptor alpha) and ROR γt, were reduced by IL-35 treatment. In conclusion, IL-35 reduced level of IL-17 and inhibited Th17 differentiation to protect against PDR.

Osteoporosis is a common metabolic bone disease mainly involving bone remodeling and blood vessels. The current study aimed to explore the suppressive role of interleukin (IL)-35 in nuclear factor kappa-B ligand receptor activator (RANKL) and macrophage colony stimulating factor (M-CSF)-induced osteoclastogenesis and angiogenesis in osteoclasts.

Th17 cells, a CD4+ T-cell subset, produce interleukin (IL)-17, a pro-inflammatory cytokine that has been shown to be involved in several forms of infectious and noninfectious uveitis. Here, we explore the roles of this IL in uveitic disorders as well as in experimental autoimmune uveitis, the possible pathogenic implications of several cytokines associated with IL-17 and analyze the current outcomes and goals for drugs aiming for the IL-17 pathway.

Interleukin 17(A) (IL-17) is a potent pro-inflammatory cytokine that acts as a central regulator of inflammatory response within the brain, but its physiological roles under non-inflammatory conditions remain elusive. Here we report that endogenous IL-17 ablates neurogenesis in the adult dentate gyrus (DG) of hippocampus. Genetic deletion of IL-17 increased the number of adult-born neurons in the DG. Further, we found that IL-17 deletion altered cytokine network, facilitated basal excitatory synaptic transmission, enhanced intrinsic neuronal excitability, and increased expression of proneuronal genes in neuronal progenitor cells (NPCs). Our findings suggest a profound role of IL-17 in the negative regulation of adult hippocampal neurogenesis under physiology conditions.

Acute cellular rejection of organ transplants is executed by donor-reactive T cells, which are dominated by interferon-gamma-producing cells. As interferon-gamma is dispensable for graft destruction, we evaluated the contribution of interleukin-17A (IL-17) to intragraft inflammation in major histocompatibility complex-mismatched heart transplants. A/J (H-2(a)) cardiac allografts placed into wild-type BALB/c (H-2(d)) mice induced intragraft IL-17 production on day 2 after transplant. Allografts placed into BALB/c IL-17(-/-) recipients demonstrated diminished production of the chemokines CXCL1 and CXCL2 and delayed neutrophil and T cell recruitment. However, by day 7 after transplant, allografts from IL-17(-/-) and wild-type recipients had comparable levels of cellular infiltration. The priming of donor-specific T cells was not affected by the absence of IL-17, and the kinetics of cardiac allograft rejection were similar in wild-type and IL-17(-/-) recipients. In contrast, IL-17(-/-) mice depleted of CD8 T cells rejected A/J allografts in a delayed fashion compared with CD8-depleted wild-type recipients. Although donor-reactive CD4 T cells were efficiently activated in both groups, the infiltration of effector T cells into allografts was impaired in IL-17(-/-) recipients. Our data indicate that locally produced IL-17 amplifies intragraft inflammation early after transplantation and promotes tissue injury by facilitating T cell recruitment into the graft. Targeting the IL-17 signaling network in conjunction with other graft-prolonging therapies may decrease this injury and improve the survival of transplanted organs.

The present study aimed to examine the correlation between serum cytokine levels and the incidence of coronary artery disease (CAD), a leading cause of mortality globally, which is known to have a strong association with inflammatory factors. The study further sought to determine the predictors of CAD to distinguish patients with coronary artery lesions from those suspected of having CAD.

Pro-inflammatory cytokines are known to have deleterious effects on Schwann cells (SCs). Interleukin 17 (IL-17) is a potent pro-inflammatory cytokine that exhibits relevant effects during inflammation in the peripheral nervous system (PNS), and IL-17-secreting cells have been reported within the endoneurium in proximity to the SCs.

Interleukin-17 (IL-17) is a cytokine secreted by a variety of immune cells that plays an important role in host defense against pathogens. IL-17 usually activates downstream immune signaling pathway by binding to heterodimeric or homodimeric complex formed by IL-17 receptors (IL-17R). Describing the characteristics, tissue distribution of IL-17 and IL-17 receptor family members and their expression after pathogen infection will provide a reference for host defense against disease of turbot. In this study, six IL-17 family members and nine IL-17 receptor family members were identified by analyzing the turbot (Scophthalmus maximus) genome. Different from other vertebrates, most members of the IL-17 receptor family own two copies. Protein structure analysis showed that the six IL-17 family members contained typical "IL-17" domains, and the nine IL-17 receptor family members contained typical "SEFIR domain" or "IL17_R_N domain". Syntenic analysis revealed that all IL-17s and IL-17Rs were chromosomally conserved compared with other fish. The phylogenetic analysis further confirmed the evolutionary conservatism of different copies of IL-17C and IL-17Rs. Tissue distribution results showed that IL-17 and IL-17R genes were highly expressed in immune-related tissues. The expression of IL-17C and its receptor in the mucosal immune tissues after infection with V. anguillarum were analyzed subsequently, which were significantly increased in the skin. The results are consistent with previous studies showing that IL-17 and IL-17 receptor play an important role in promoting innate immune response.

Vibrio harveyi is regarded as serious pathogen for marine fishes. To evaluate the physiological responses of spotted sea bass (Lateolabrax maculatus) after V. harveyi infection, four biochemical biomarkers including alanine amino transferase (ALT), albumin (ALB), total protein (TP) and glucose (GLU) were measured in serum. Our results showed that V. harveyi infection significantly influenced the concentration of ALT, ALB and GLU. Additionally, five interleukin-17 (IL-17) and five IL-17 receptors (IL-17R) genes were identified in spotted sea bass and their gene structures were characterized. Furthermore, the expression patterns of IL-17 and IL-17R genes were determined by qPCR in liver, intestine, spleen and head kidney after V. harveyi infection. All IL-17 and IL-17R genes exhibited time- and tissue-dependent expressions. Several tested genes were dramatically induced by V. harveyi treatment, particularly IL-17A/F1 in liver and head kidney, IL-17A/F2 in head kidney, IL-17RC in spleen with more than 10-fold increases, which suggested their potential essential roles against bacterial infection.

Fibrosis affects all vital organs accounting for a staggering 45% of deaths worldwide and no effective therapies are currently available. Unresolved inflammation triggers downstream signaling events that lead to organ fibrosis. In recent years, proinflammatory cytokine Interleukin-17 (IL-17) has been implicated in several chronic inflammatory diseases that often culminate in organ damage followed by impaired wound healing and fibrosis. In this review, we outline the contribution of the IL-17 in mediating fibrotic diseases in various organs. A comprehensive understanding of the inflammatory events, and particularly the details of IL-17 signaling in vivo, could be beneficial in designing new therapeutic or preventive approaches to treat fibrosis. Additionally, understanding organ-specific differences in IL-17 activity could lead to targeted therapies and help spare other organs from unwanted side effects.

Mammalian cells autonomously activate hypoxia-inducible transcription factors (HIFs) to ensure survival in low-oxygen environments. We report here that injury-induced hypoxia is insufficient to trigger HIF1α in damaged epithelium. Instead, multimodal single-cell and spatial transcriptomics analyses and functional studies reveal that retinoic acid-related orphan receptor γt+ (RORγt+) γδ T cell-derived interleukin-17A (IL-17A) is necessary and sufficient to activate HIF1α. Protein kinase B (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling proximal of IL-17 receptor C (IL-17RC) activates mammalian target of rapamycin (mTOR) and consequently HIF1α. The IL-17A-HIF1α axis drives glycolysis in wound front epithelia. Epithelial-specific loss of IL-17RC, HIF1α, or blockade of glycolysis derails repair. Our findings underscore the coupling of inflammatory, metabolic, and migratory programs to expedite epithelial healing and illuminate the immune cell-derived inputs in cellular adaptation to hypoxic stress during repair.

IL-17 is one of the most potent and most actively investigated proinflammatory cytokines. In this study, we examined the effect of IL-17 on mesenchymal stem cells (MSCs) under the influence of inflammatory cytokines. Ironically, IL-17 dramatically enhanced the immunosuppressive effect of MSCs induced by IFNγ and TNFα, revealing a novel role of IL-17 in immunosuppression. Interestingly, we found that this action of IL-17 was dependent on the promoted expression of a key immune suppressive molecule, inducible nitric oxide synthase (iNOS), in MSCs. In a concanavalin A (ConA)-induced hepatitis mouse model, we found that IL-17 also enhanced the in vivo immunosuppressive effect of MSCs in an iNOS-dependent manner. Moreover, this promoting effect of IL-17 was found to be exerted through enhancing mRNA stability by modulating the protein level of ARE/poly(U)-binding/degradation factor 1 (AUF1), a well-known factor that promotes mRNA decay. In auf1(-/-) MSCs, IFNγ and TNFα could induce maximal immunosuppressive effect, both in vitro and in vivo, without the need for IL-17. Thus, our studies demonstrated that in the presence of MSCs, IL-17 promotes immunosuppression.

To explore the process of pressure ulcer formation, interleukin (IL)-17 expression levels were observed in a mouse model of pressure ulcers. Twenty mice were divided into experimental and control groups (10 mice per group). A mouse model of pressure ulcers was established by inducing ischemia-reperfusion injury on local tissue in the experimental group. Pressure ulcer tissues in the experimental group and normal mouse tissue in the control group were stained using hematoxylin and eosin (H&E) and observed using light microscopy. The protein and mRNA expression levels of IL-17, in mouse pressure ulcer tissues from the experimental group and in the normal tissue from the control group, were determined using real-time PCR and western blot analysis, respectively. The mRNA and protein expression levels of IL-17 were compared between the two groups. H&E staining indicated that striated muscle was arranged orderly and cellular structure was intact in the control group, whilst inflammatory cell infiltration was observed in the muscle tissue of the experimental group. The expression levels of IL-17 mRNA were 0.307±0.058 ng in the experimental group and 0.112±0.042 ng in the control group (P<0.05). The expression levels of the IL-17 protein were 0.434±0.097 ng in the experimental group and 0.181±0.040 ng in the control group (P<0.05). IL-17 expression levels were increased in pressure ulcers, which suggests that IL-17 may be associated with pressure ulcers.

Alphaviral arthritides caused by mosquito-borne arboviruses such as chikungunya virus (CHIKV) can persist for months after the initial acute disease. Here, we investigated the contribution of interleukin-17 (IL-17), a cytokine involved in chronic autoimmune arthropathies such as rheumatoid arthritis, to the development of alphaviral arthropathy. Sera from CHIKV-infected patients who displayed both acute and chronic disease showed high levels of IL-17, IL-6, IL-21, IL-22, and IL-23, especially during the chronic phase of disease. We sought to validate these findings using a mouse model of CHIKV infection and disease using wild-type and IL-17A-deficient mice. Mice were infected with CHIKV, and joint and muscle tissues were harvested at designated time points. Tissue infiltrates were examined by immunohistochemistry, and tissue mRNA and protein expression of cytokines was assessed. Joint and muscle pathology was assessed using histology. CHIKV-infected mice lacking IL-17A showed reduced tissue inflammation and neutrophil infiltration, compared to wild-type mice. These investigations showed a role for IL-17 in the acute phase of CHIKV infection and also during the postacute disease resolution phase. IMPORTANCE CHIKV has been prevalent in Africa, Asia, and the Indian Ocean Islands for decades. There are currently no clinically approved vaccines or specific antiviral drugs targeting CHIKV. The upregulation of IL-17 detected in CHIKV disease patients and the reduced disease seen in IL-17-deficient mice suggest a correlation between IL-17 signaling pathways and CHIKV-induced arthritic inflammation. With an established role in contributing to the pathogenesis of immune-mediated diseases, such as psoriatic arthritis and rheumatoid arthritis, IL-17 signaling plays an important role in alphavirus arthritides.

Osteoarthritis (OA), which is the most common degenerative joint disorder, has been considered a non-inflammatory disease with abnormal mechanics. Interleukin (IL)-17 is a pleiotropic cytokine involved in inflammatory diseases and their production is driven by the cytokine including IL-1 and IL-23. However, little is known about the mechanism of IL-17 in the development of OA. Here, we investigated the role of IL-17 in the pathogenesis of OA using monosodium iodoacetate (MIA)-injected IL-17 and IL-1 receptor antagonist (IL-1Ra) double-deficient mice. In MIA-injected IL-1Ra KO mice, nociceptive properties, degree of cartilage damage, and the level of inflammatory factors in articular cartilage were increased compared to MIA-injected wild-type mice. Interestingly, the intestinal architecture was impaired in IL-1Ra KO mice compared to wild-type mice and the damage was further exacerbated by MIA injection. Deficiency of IL-17 reduced nociceptive properties and cartilage destruction, as well as inflammation-related factors in MIA-injected IL-1Ra KO mice compared to MIA-injected wild-type mice. Furthermore, IL-17-treated chondrocytes from OA patients showed enhanced expression of catabolic factors that are involved in the destruction of cartilage in OA. IL-17 accelerates the destruction of cartilage and small intestine via regulation of several inflammatory mediators in an OA murine model. These results suggest that IL-17 plays a critical role in the development of OA.

Chronic periodontitis is an inflammatory condition of the tooth supporting structures. There is increasing evidence that the cytokines interleukin-17 (IL-17) and interleukin-18 (IL-18) play a role in progression of chronic periodontitis.

This study investigated the correlation between the levels of interleukin (IL)-17 and IL-18 and atherosclerotic plaques. A total of 60 Apo E gene (Apo E-/-) mice were fed with high-fat diet in the model group and 20 wild male C57BL/6 mice were fed with the basic diet in the control group. The serum levels of IL-17 and IL-18 were determined by enzyme-linked immunosorbent assay. Carotid artery ultrasonography was performed and divided into stable plaque, unstable plaque and non-plaque groups. The severity of plaque was estimated by semi-quantitative method and divided into grades I, II and III. The expression levels of low-density lipoprotein cholesterol, plasma total cholesterol and blood glucose level in the model group induced by high-fat diet were significantly higher than those in the control group (P<0.05). The level in the model group was significantly higher than in the control group at the 16th week (P<0.05). The expression of IL-17 and IL-18 in the model group was significantly higher than that in the control group (t=6.903, 11.02, P<0.05). The concentration of IL-17 and IL-18 in the non-plaque group was significantly lower than that in the stable plaque and unstable plaque groups (P<0.05). The concentration of IL-17 and IL-18 in the stable plaque group was significantly lower than that in the unstable plaque group (P<0.05). Based on the correlation of IL-17 and IL-18 expressions in the model group, the expression of IL-18 increased with the expression of IL-17, indicating that the expression of IL-17 was positively correlated with that of IL-18 (r=0.7195, P<0.001). In conclusion, serum IL-17 and IL-18 played an important role in the formation and development of atherosclerotic plaque, and were related to the stability and severity of plaque. The expression of IL-17 and IL-18 was positively correlated.

Periimplant diseases are inflammatory diseases. Thus, the level of preinflammatory cytokines which has important role in the inflammation processes can consider as biomchemical markers for early diagnosis and prevention of periimplant diseases. The aim of this study was to determine and compare the level of interleukin (IL)-17 and IL-10 in patients with periimplant mucositis and periimplantitis.

"Psoriasis" is a chronic immune-mediated inflammatory disorder with epidermal hyperplasia. There is some evidence that the cytokine interleukin-17A (often known as IL-17), which is mainly produced by Th17 cells, has a role in the pathogenesis of psoriasis. "IL-17" is a pro-inflammatory cytokine mainly important in the host's defense against extracellular bacteria and fungi. The three new therapies with biologic drugs - brodalumab, secukinumab, and ixekizumab - all target the IL-17 signaling pathway. Secukinumab and ixekizumab neutralize IL-17A, while brodalumab blocks its receptor. Results from clinical trials have shown marked improvements in disease severity in patients with moderate-to-severe plaque psoriasis, using any of these three drugs. The biologic agents were generally well tolerated, but the duration of the trials was relatively short. In this review, we focus on the role of the IL-17 cytokine family in the pathogenesis of psoriasis; the efficacy, safety, and tolerability of brodalumab, secukinumab, and ixekizumab in clinical trials; and possible differences between targeting of the IL-17A receptor and targeting of the IL-17A ligand.

Interleukin-17 (IL-17) is expressed in the intestine in response to changes in the gut microbiome landscape and plays an important role in intestinal and systemic inflammatory diseases. There is evidence that dietary factors can also modify the expression of intestinal IL-17. Here, we hypothesized that, similar to several other gut-produced factors, IL-17 may act in the hypothalamus to modulate food intake. We confirm that food intake increases IL-17 expression in the mouse ileum and human blood. There is no expression of IL-17 in the hypothalamus; however, IL-17 receptor A is expressed in both pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons. Upon systemic injection, IL-17 promoted a rapid increase in hypothalamic POMC expression, which was followed by a late increase in the expression of AgRP. Both systemic and intracerebroventricular injections of IL-17 reduced calorie intake without affecting whole-body energy expenditure. Systemic but not intracerebroventricular injection of IL-17 increase brown adipose tissue temperature. Thus, IL-17 is a gut-produced factor that is controlled by diet and modulates food intake by acting in the hypothalamus. Our findings provide the first evidence of a cytokine that is acutely regulated by food intake and plays a role in the regulation of eating.