Th17 Axis Research Articles

Behçet's syndrome: one year in review 2024.

The aim of this review is to provide a critical summary of studies published during 2023 that contribute to our understanding of Behçet's syndrome. An increase in the incidence of BS was reported in Northern Spain after 2014.Studies on patient perspectives showed the impact of Behçet's syndrome on quality of life, daily activities, education, work, and relationships. Differences in genetics among Behçet's syndrome patients with different types of organ involvement were reported and an association between HLA-B/MICA and SLCO4A1 polymorphisms and eye involvement and between DDX60L polymorphisms and nervous system involvement were observed. It was suggested that Integrin α9β1 plays a crucial role in the neutrophil-mediated inflammatory pathways underlying this syndrome and the dysfunction of the PDL1/PD-1 pathway may be associated with the hyperactivity of the Th-1/Th-17 axis. Vein wall thickness seems to be increased in patients with Behçet's syndrome, but its pathogenetic and clinical implications are not clear. There is growing evidence regarding the efficacy of TNF inhibitors in different types of organ involvement. A number of small case series point out to the potential role of TCZ and JAK inhibitors.

Expanding the frontiers of therapeutic options in hidradenitis suppurativa: The valid contribution of bimekizumab

Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disorder with a significant negative impact on quality of life. Th17 axis has a central role in the pathogenesis of HS. Kimball etal. demonstrated the efficacy and safety of bimekizumab in two double-blind, placebo-controlled phase 3 studies (BE HEARD I-II), adding a new targeting option to the therapeutic armamentarium of HS.1.

689 - Unmet needs of managing atopic dermatitis: where do we stand in modifying vs. suppressing disease?

Abstract Introduction Atopic Dermatitis (AD) is a chronic relapsing inflammatory skin condition that is evolvingly perceived as a systemic disease, particularly when severe. The therapeutic ladder for managing AD has undergone substantial expansion in the last decade as new pathways are revealed, yet 75% of patients are not satisfied with their management of AD. While patients may report symptom relief, AD often requires ongoing treatment, increased dosage, or alternating regimens. For those patients who appear to respond well over a prolonged period, it is unclear whether they will tolerate treatment cessation. Objective To evaluate the current therapeutic options available for AD from the standpoint of their disease-modifying vs. disease-suppressing capabilities. Methods A systematic review of the literature was performed using academic research databases including PubMed and Embase between 1994 and 2024. The studies extracted from the search included, but were not limited to, randomized placebo-controlled trials, systematic reviews, cross-sectional studies, observational studies, case series, case reports, and retrospective studies. Current and emerging therapies for the treatment of AD were assessed for their ability to modify underlying disease mechanisms, and/or induce disease remission. Results Although several of the drugs that are currently approved for AD target the pathogenic Th2 axis, Janus Kinase (JAK) inhibitors have the most supporting evidence for their ability to modify underlying disease mechanisms. Inhibiting distinct JAK families hinders the downstream effects of multiple cytokines involved in AD at once. In some case reports, patients treated with selective JAK-1 inhibitors for up to 6 months did not experience disease recurrence following cessation during a several-month follow-up period. Similar studies of certain biological agents have shown prolonged periods of remission after discontinuation of dupilumab, tralokinumab, and lebrikizumab. This suggests that they may also drive long-lasting cellular changes, especially when implemented in early disease. Targeting OX40 or its ligand, the OX40L, may also hold promise for modifying AD. Studies have additionally indicated that there may be a therapeutic window of opportunity for maximal treatment impact in AD. Early intervention shortly after pediatric onset of disease may lead to improved long-term control and reduced comorbidity development. Novel disease-modifying strategies are currently being investigated in clinical trials for their capacity to correct skin and gut dysbiosis, restore epidermal barrier integrity, and alter innate and adaptive immune responses. Conclusions Recent progress in drug development has greatly advanced symptom control in patients with AD. However, only a few, if any, therapeutic strategies have demonstrated long-term disease modification. There is an unmet need to study the rate of recurrence upon cessation of current AD therapies. Future research should prioritize the development of therapeutic interventions for AD that not only treat symptoms but also modify the underlying disease pathology over time.

Activation of the interleukin-23/Th17 axis in major depression: a systematic review and meta-analysis.

The interleukin-23/Th17 axis is a promising modifiable target for depression. However, its association with depression has not been systematically evaluated. We systematically searched four databases (EMBASE, Web of Science, Pubmed and PsycINFO) for studies comparing patients with major depression and healthy controls for plasma/serum levels of Th17 cells and their canonical cytokines (interleukin-17A [IL-17A], IL-22, granulocyte macrophage colony stimulating factor [GM-CSF]). We also compared counts of Th1, Th2 and Th9 cells between depressed/non-depressed patients and their respective canonical cytokines. We performed random-effects meta-analysis of the standardised mean difference (SMD) in immune measures between groups. Risk of bias was assessed using the Newcastle-Ottawa scale. Of 3154 studies screened, 36 studies were included in meta-analysis. Patients with depression had elevated IL-17A compared to controls (SMD = 0.80 [95% CI 0.03 to 1.58], p = 0.042), an association moderated by antidepressant use (Z = 2.12, p = 0.034). Patients with depression had elevated GM-CSF (SMD = 0.54 [95% CI 0.16 to 0.91], p = 0.0047), and a trend towards higher Th17 counts (SMD = 0.44 [-0.01 to 0.88], p = 0.052). Whilst the Th2-associated cytokine IL-5 was elevated in depression (SMD = 0.36 [95% CI 0.05 to 0.66], p = 0.02), Th2 cell counts (p = 0.97), Th1 cell counts (p = 0.17) and interferon-γ (p = 0.22) were not. Data for Th9 cells, IL-9 and IL-22 were insufficient for meta-analysis. Respectively, 22, 25 and 5 studies were good, fair and poor in quality. Patients with major depression show peripheral over-activation of the IL-23/Th17 axis. Future interventional studies should test whether this is a modifiable target for depression.

Improvement effects of a novel Chinese herbal formula in imiquimod and IL-23-stimulated mouse models of psoriasis

BackgroundPsoriasis is a long-term inflammatory skin disease. A novel herbal formula containing nine Chinese herbal medicines, named Inflammation Skin Disease Formula (ISDF), has been prescribed in clinics for decades.AimsTo investigate the efficacy and action mechanisms of ISDF on psoriasis using imiquimod (IMQ) and Interleukin-23 (IL-23)-induced models in mice and reveal the pharmacokinetics profile of ISDF in rats.MethodsTopical administration of IMQ and intradermal injection with IL-23 respectively induced skin lesions like psoriasis on the dorsal area of Balb/c and C57 mice. The mice's body weight, skin thickness, and psoriasis area and severity index (PASI) were assessed weekly. SD rats were used in the pharmacokinetics study and the contents of berberine and baicalin were determined.ResultsThe PASI scores and epidermal thickness of mice were markedly decreased after ISDF treatment in both models. ISDF treatment significantly decreased the contents of IL-17A and IL-22 in the serum of IMQ- and IL-23-treated mice. Importantly, ISDF markedly downregulated IL-4, IL-6, IL-1β, and tumor necrosis factor α (TNF-α) gene expression, and the phosphorylation of NF-κB p65, JNK, ERKs and MAPK p38 in IMQ-treated mice. The protein phosphorylation of Jak1, Jak2, Tyk2 and Stat3 was significantly mitigated in the ISDF-treated groups. The absorption of baicalin and berberine of ISDF through the gastrointestinal tract of rats was limited, and their distribution and metabolism in rats were also very slow, which suggested ISDF could be used in the long-term application.ConclusionsISDF has a strong anti-psoriatic therapeutic effect on mouse models induced with psoriasis through IMQ and IL-23, which is achieved by inhibiting the activation of the Jak/Stat3-activated IL-23/Th17 axis and the downstream NF-κB signalling and MAPK signalling pathways. ISDF holds great potential to be a therapy for psoriasis and should be further developed for this purpose.

Fungal Head and Neck Dermatitis: Current Understanding and Management.

Head and neck dermatitis (HND) is a form of atopic dermatitis (AD) that affects the seborrheic areas of the body and causes greater quality of life detriments than other types of AD. HND can be challenging to treat since first-line topical therapies may be ineffective or intolerable for long-term use on areas affected by HND while dupilumab may cause dupilumab-associated HND (DAHND). Current evidence implicates fungi, particularly Malassezia spp., in the pathogenesis of HND. Penetration of fungal antigens through the defective AD skin barrier activates the innate and adaptive immune systems to cause cutaneous inflammation via the T helper (Th)17 and/or Th2 axes. Malassezia sensitization may distinguish HND from other forms of AD. Multiple double-blind, placebo-controlled trials have shown antifungals to benefit HND, yet the persistence of symptom reliefwith sustained use remains unclear. Oral antifungals appear more effective than topical antifungals but may be harmful with long-term use. DAHND may also be fungal-mediated given improvement with antifungals and evidence of an overactive immune response against Malassezia in these patients. Janus kinase inhibitors are effective for HND, including DAHND, but may cause significant side effects when administered systemically. OX40/OX40L inhibitors and tralokinumab may be promising options for HND on the horizon. Demographic and environmental factors influence the host mycobiome and should be considered in future precision-medicine approaches as microbiome composition and diversity are linked to severity of HND.

Functional Genomics and Insights into the Pathogenesis and Treatment of Psoriasis.

Psoriasis is a lifelong, systemic, immune mediated inflammatory skin condition, affecting 1-3% of the world's population, with an impact on quality of life similar to diseases like cancer or diabetes. Genetics are the single largest risk factor in psoriasis, with Genome-Wide Association (GWAS) studies showing that many psoriasis risk genes lie along the IL-23/Th17 axis. Potential psoriasis risk genes determined through GWAS can be annotated and characterised using functional genomics, allowing the identification of novel drug targets and the repurposing of existing drugs. This review is focused on the IL-23/Th17 axis, providing an insight into key cell types, cytokines, and intracellular signaling pathways involved. This includes examination of currently available biological treatments, time to relapse post drug withdrawal, and rates of primary/secondary drug failure, showing the need for greater understanding of the underlying genetic mechanisms of psoriasis and how they can impact treatment. This could allow for patient stratification towards the treatment most likely to reduce the burden of disease for the longest period possible.

The Role of Interleukin 23/17 Axis in Psoriasis Management: A Comprehensive Review of Clinical Trials.

Psoriasis pathogenesis is influenced by genetic factors and characterized by a complex interplay between genetic predisposition and various environmental triggers. These triggers set off metabolic processes involving inflammation, cell signaling, immune response dysregulation, and antigen presentation. Several types of innate and adaptive immune cells are involved in psoriasis. Among the cytokine cascade which leads to psoriasis development, the interleukin (IL)-23/Th17 axis, especially IL-17 production, emerges as crucial. Recognizing the pivotal role of this axis has facilitated the development of selective and effective biological drugs, such as anti-IL17 and anti-IL23 monoclonal antibodies. These drugs aim to achieve the complete or near-complete disappearance of psoriatic lesions, as indicated by PASI100 and PASI90 responses, respectively. In this context, the aim of our review was to delve into the functioning of the IL-23/Th17 axis, its dysregulation in psoriasis pathogenesis, and the therapeutic potential of its inhibition. Currently, 4 anti-IL17 (secukinumab, ixekizumab, bimekizumab and brodalumab) and 3 anti-IL23 (guselkumab, risankizumab and tildrakizumab) have been approved. All these drugs showed high levels of effectiveness in both clinical trials and real-life experiences, with an excellent profile in terms of safety. Certainly, furthers studies will allow for better characterization of biologics' profile, in order to administer the right drug for the right patients at the right moment.

Allosterically activating SHP2 by oleanolic acid inhibits STAT3–Th17 axis for ameliorating colitis

Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) is an essential tyrosine phosphatase that is pivotal in regulating various cellular signaling pathways such as cell growth, differentiation, and survival. The activation of SHP2 has been shown to have a therapeutic effect in colitis and Parkinson's disease. Thus, the identification of SHP2 activators and a complete understanding of their mechanism is required. We used a two-step screening assay to determine a novel allosteric activator of SHP2 that stabilizes it in an open conformation. Oleanolic acid was identified as a suitable candidate. By binding to R362, K364, and K366 in the active center of the PTP domain, oleanolic acid maintained the active open state of SHP2, which facilitated the binding between SHP2 and its substrate. This oleanolic acid-activated SHP2 hindered Th17 differentiation by disturbing the interaction between STAT3 and IL-6Rα and inhibiting the activation of STAT3. Furthermore, via the activation of SHP2 and subsequent attenuation of the STAT3–Th17 axis, oleanolic acid effectively mitigated colitis in mice. This protective effect was abrogated by SHP2 knockout or administration of the SHP2 inhibitor SHP099. These findings underscore the potential of oleanolic acid as a promising therapeutic agent for treating inflammatory bowel diseases.

The Dysregulated IL-23/TH17 Axis in Endometriosis Pathophysiology.

Endometriosis is a chronic inflammatory disease in which endometrial-like tissue grows ectopically, resulting in pelvic pain and infertility. IL-23 is a key contributor in the development and differentiation of TH17 cells, driving TH17 cells toward a pathogenic profile. In a variety of inflammatory and autoimmune disorders, TH17 cells secrete proinflammatory cytokines, including IL-17, contributing to disease pathophysiology. Our studies and others have implicated IL-17 and TH17 cell dysregulation in endometriosis, which is associated with disease severity. In this article, we address whether IL-23-driven TH17 cells contribute to cardinal features of lesion proliferation, vascularization, and inflammation in endometriosis using patient samples, representative cell lines, and our established mouse model of endometriosis. The results indicated dysregulated expression of key genes in the IL-23/TH17 axis in patient ectopic and eutopic endometrial samples and increased IL-23 protein in patient plasma compared with controls. In vitro studies using primary human TH cells determined that rIL-23 mixture treatment increased pathogenic TH17 cell frequency. Similarly, rIL-23 treatment of cell lines (12Z cells, EECCs, HUVECs, and hESCs) representative of the endometriotic lesion microenvironment increased cytokines and growth factors, which play a role in lesion establishment and maintenance. In a syngeneic mouse model of endometriosis, rIL-23 treatment altered numbers of myeloid and T cell subsets in peritoneal fluid and increased giant cells within the lesion. Lesions from rIL-23-treated mice did not reveal significant alterations in proliferation/vascularization, although trends of increased proliferation and vascularization were observed. Collectively, these findings provide insights into the impact of the IL-23/TH17 axis on local immune dysfunction and broadly on endometriosis pathophysiology.

Traditional Chinese Medicine Shi-Bi-Man ameliorates psoriasis via inhibiting IL-23/Th17 axis and CXCL16-mediated endothelial activation

BackgroundPsoriasis is a chronic inflammatory genetic disease, mainly manifesting in the skin. Conventional therapies, such as glucocorticosteroids and corticosteroids, have adverse effects that limit drug use. Hence, it is imperative to identify a new therapeutic strategy that exhibits a favorable safety profile. Shi-Bi-Man (SBM) is a safe herbal supplement sourced from various natural plants, including ginseng, angelica sinensis, polygonum multiflorum, and aloe vera.PurposeWe aimed to find a potential treatment for psoriasis and investigate the underlying mechanism through which SBM alleviates psoriatic-like skin inflammation in mice.MethodsWe investigated the effects of supplementing with SBM through intragastric administration or smear administration in a murine model of imiquimod-induced psoriasis. The changes in body weight and Psoriasis Area and Severity Index (PASI) score were recorded throughout the entire process. Additionally, we used hematoxylin–eosin staining to observe the skin structure and performed single-cell RNA sequencing to explore the underlying mechanism of SBM in influencing the psoriasis-like phenotype. Immunofluorescence was conducted to verify our findings. Furthermore, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to investigate the impact of Tetrahydroxy stilbene glycoside (TSG) on the expression levels of IL23 in HaCaT cells.ResultsSBM remarkably alleviated the psoriasis-like phenotype by inhibiting IL-23/Th17 cell axis. Single-cell RNA sequencing analysis revealed a decrease in the expression of Il17 and Il23 in keratinocytes and T cells, concomitant with a reduction in the proportion of Th17 cells. Meanwhile, the activation of endothelial cells was inhibited, accompanied by a decrease in the expression of Cxcl16. In vitro, the addition of TSG to HaCaT cells resulted in significant suppression of IL23 expression stimulated by tumor necrosis factor-alpha (TNF-α).

Dupliumab therapy for alopecia areata: a case series and review of the literature

Background A growing body of research supports the important role of the TH2 axis in alopecia areata (AA). Dupilumab is a humanized monoclonal antibody against IL-4Rα that downregulates TH2 response. Although efficacy has been shown in clinical trials, real-world data on the use of dupilumab in AA patients is limited. Objectives To report on a case series of 10 patients with AA who were treated with dupilumab and provide real-world evidence regarding its efficacy in treating severe AA. Methods In this retrospective single-center study, all AA patients treated with dupilumab treatment were included between May 2022 and October 2023. Clinical outcome measures (Severity of Alopecia Tool, SALT) and adverse events (AEs) were analyzed. In addition, a literature review was conducted to summarize the efficacy of AA with dupilumab and the characteristics of patients previously reported in the literature. Results We identified 10 patients with AA who were or are being treated with dupilumab, with a median (range) treatment duration of 8 (3-15) months. Of these, four patients have high serum immunoglobulin E (IgE) levels (≥200IU/ml). The mean (IQR) pretreatment SALT score was 79% (52-100). Seven of 10 patients achieved at least 50% re-growth. Of those who improved, the mean (IQR) percentage change in SALT score at 3 months and the end of follow-up was 57% (29%-89%) and 95% (68-100), respectively. Notably, seven patients (70%) had white hair regrowth, with the white hair slowly decreasing over time and the proportion of pigmented black hair increasing. Dupilumab was well tolerated by all patients. No adverse events were reported. Conclusions Overall, our research supports dupilumab as another candidate that possesses potential benefits for AA. High levels of IgE may be not prerequisites for dupilumab’s successful treatment response.

Unraveling the gut microbiota's role in salt-sensitive hypertension: current evidences and future directions.

The gut microbiota plays a pivotal role in both maintaining human health and in the pathogenesis of diseases. Recent studies have brought to light the significant correlation between gut microbiota and hypertension, particularly focusing on its role in the development and advancement of SSH, a subtype characterized by elevated blood pressure in response to high salt consumption. The complexity of SSH's etiology is notable, with dysbiosis of the gut microbiome identified as a crucial contributing factor. The gut microbiota participates in the occurrence and development of SSH by affecting the host's immune system, metabolic function, and neuromodulation. Investigations have demonstrated that the gut microbes regulate the development of SSH by regulating the TH17 axis and the activity of immune cells. Moreover, microbial metabolites, such as short-chain fatty acids, are implicated in blood pressure regulation and affect the development of SSH. There is evidence to show that the composition of the gut microbiome can be altered through prebiotic interventions so as to prevent and treat SSH. This review aims to concisely sum up the role of gut microbiota in SSH and to discuss pertinent therapeutic strategies and clinical implications, thereby providing a valuable reference for further research and clinical practice in this area.

Carrot Juice Intake Affects the Cytokine and Chemokine Response in Human Blood after Ex Vivo Lipopolysaccharide-Induced Inflammation

In vitro and animal studies have shown that carrot juice containing bioactive natural products, such as falcarinol (FaOH) and falcarindiol (FaDOH), can affect inflammation. The present study was designed to test whether oral intake of carrot juice containing the bioactive acetylenic oxylipins FaOH and FaDOH affects mediators of acute inflammation or the innate immune response in human blood. Carrot juice (500 mL) was administered orally to healthy volunteers, and blood samples were drawn before and 1 h after juice intake. Next, the blood samples were split in two, and one sample was stimulated ex vivo with lipopolysaccharide (LPS) and incubated at 37 °C for 24 h. The concentrations of 44 inflammatory cytokines and chemokines were examined using multiplex electrochemiluminescence analysis. In blood samples not stimulated with LPS, a significant increase in IL-15 was measured 1 h after carrot juice intake. Cytokines like IFN-ɣ, IL-12/IL-23(p40), IL-23, IL-17A, IL-17B, IL-17D, and IL-22 were significantly increased in LPS-stimulated blood samples after carrot juice intake. The upregulation of the immunostimulating cytokines belonging to the IL-23/IL-17 Th17 axis suggests that carrot juice intake could benefit diseases where inflammation plays a role, like in the early stages of diabetes or cancers.

Association of Serum IL-17 and IL-23 Cytokines With Disease Activity and Various Parameters of Rheumatoid Arthritis in Indian Patients.

Introduction Interleukin-23/T helper 17 (IL-23/Th17) axis cytokine has been thought to be a critical pathway for rheumatoid arthritis (RA) disease development and its association with disease severity, joint erosion, and functional outcome. There is a paucity of data on the role of IL-23/Th17 axis cytokines in an Indian RA subset of patients. We aimed to determinethe association between serum cytokines (interleukin-17 [IL-17] and [IL-23]) and disease activityas well as with clinical and biochemical parameters of RA patients. Methods In this observational cross-sectional study, 84 consecutive RA cases were recruited after obtaining consent. Serum IL-17 and IL-23 levels were measured by the enzyme-linked immunosorbent assay (ELISA) method. Clinical and laboratory parameters, disease activity score 28-erythocyte sedimentation rate (DAS28-ESR), and Health Assessment Questionnaire-II (HAQ-II) were recorded. Correlation of cytokines with various clinical and biochemical parameters was elicited. Results Only C-reactive protein (CRP) correlated positively with IL-23 (rs = 0.26, p = 0.014)but not the ESR. Both IL-17 and IL-23 levels showed an insignificant, weak positive correlation with the disease activity DAS28 (rs = 0.18, p = 0.097; rs = 0.12, p = 0.259, respectively). Neither IL-17 nor IL-23 levels differed among the disease severity group (p = 0.13, p = 0.215). Only the IL-23 level positively correlated with functional status (HAQ-II) (rs = 0.28, p = 0.009). IL-17 level was higher in advanced RA as compared to early RA (p = 0.028). Both IL-17 and IL-23 levels did not vary within the different subgroups (age, obesity, disease-modifying drugs/steroid/biologics use, and serology status). Conclusion Females had higher IL-23 levels than males. Advanced RA had higher IL-17 levels than early RA. The cytokinelevels were not influenced by factors like age, duration of disease, serology status, or drugs. Neither of the cytokines correlated significantly with disease severity. Higher IL-17 levels may have a role in the progression of early non-erosive to chronic erosive arthritis. Higher IL-23 levels may signal a bad functional outcome.

Successful Treatment of Pityriasis Rubra Pilaris with Risankizumab in Children.

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease that affects men and women of all ages, including children. PRP is characterized by follicular and palmoplantar hyperkeratosis and salmon-colored scaling plaques. The exact pathogenesis of PRP is still unknown; most PRP cases are acquired, but some cases may show a familial occurrence, often associated with a mutation in the CARD14 gene. Due to the rarity of PRP, treatment recommendations are based mainly on case reports, small case series and expert opinions and still represent a major therapeutic challenge, especially in children. A growing number of reports on treatment with biologicals, particularly anti-TNFα, has been published. However, an involvement of the IL-23/Th17 axis in both psoriasis and PRP pathogenesis may suggest that this pathway may be a potential therapeutic target. Here, we present three pediatric patients with PRP successfully treated with risankizumab. All patients exhibited a severe course of PRP and lack of response to conventional therapy, including acitretin, cyclosporine and phototherapy. A single dose of 75 mg risankizumab resulted in almost complete clearance of skin lesions in case 1 and 2 at week 4. In patient 3, clear skin was achieved after the second administration of risankizumab (150 mg). All patients continue the treatment with risankizumab, and no adverse effects have been reported up to the present time. Our study demonstrates that risankizumab, an IL-23 blocker, shows good efficacy and safety among pediatric patients with PRP.

Molecular consideration relevant to the mechanism of the comorbidity between psoriasis and systemic lupus erythematosus (Review).

Systemic lupus erythematosus (SLE), a common autoimmune disease with a global incidence and newly diagnosed population estimated at 5.14 (range, 1.4-15.13) per 100,000 person-years and 0.40 million people annually, respectively, affects multiple tissues and organs; for example, skin, blood system, heart and kidneys. Accumulating data has also demonstrated that psoriasis (PS) can be a systemic inflammatory disease, which can affect organs other than the skin and occur alongside other autoimmune diseases, such as inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis and SLE. The current explanations for the possible comorbidity of PS and SLE include: i) The two diseases share susceptible gene loci; ii) they share a common IL-23/T helper 17 (Th17) axis inflammatory pathway; and iii) the immunopathogenesis of the two conditions is a consequence of the interactions between IL-17 cytokines with effector Th17 cells, T regulatory cells, as well as B cells. In addition, the therapeutic efficacy of IL-17 or TNF-α inhibitors has been demonstrated in PS, and has also become evident in SLE. However, the mechanisms have not been investigated. To the best of our knowledge, there remains a lack of substantial studies on the correlation between PS and SLE. In the present review, the literature, with regards to the epidemiology, genetic predisposition, inflammatory mechanisms and treatment of the patients with both PS and SLE, has been reviewed. Further investigations into the molecular pathogenic mechanism may provide drug targets that could benefit the patients with concomitant PS and SLE.

Evidence-based modalities in the management of Psoriasis and Psoriatic arthritis.

Psoriasis is a waxing and waning skin disorder, often associated with a plethora of co-morbidities, including psoriatic arthritis (PsA), a severe form of chronic inflammatory arthritis. All forms of psoriasis and PsA are immune-mediated diseases where the patient's immune system is overactive in the production of certain factors that stimulate and activate the function of certain immune cells. Recent evidence has uncovered an important role for cell-mediated immunity in the aetiology and course of psoriasis and PsA, with a critical role played by the pro-inflammatory IL-23/TH17 axis. Taken together, these new lines of evidence suggest new and improved therapeutic interventions for patients with psoriasis and PsA. The hypothesis-driven process of inquiry of the best available evidence and its implication, application and evaluation in the context of clinical practice pertains to the meta-science of evidence-based health care (EBHC). EBHC consists in the initial step of research synthesis and generation of the systematic review of the best available evidence, estimated both qualitatively and quantitatively (i.e., meta-analysis). Evidence-based decision-making, a process driven and controlled by the expertise of the clinician and by the clinical needs and personal wants of the patient, is the principal, most timely and critical aspect of evidence-based practice. Recent and systematic reviews for the treatment of psoriasis and PsA consistently updated for emerging new and revised data (i.e., living systematic reviews) confirm the efficacy and the effectiveness of methotrexate (MTX) in containing and controlling psoriasis. The outcomes of MTX intervention for PsA remain mixed and inconclusive.

The Role of IL-23 in the Pathogenesis and Therapy of Inflammatory Bowel Disease.

Interleukin-23 (IL-23) is a proinflammatory cytokine produced mainly by macrophages and antigen-presenting cells (APCs) after antigenic stimulation. IL-23 plays a significant role as a mediator of tissue damage. Indeed, the irregularities in IL-23 and its receptor signaling have been implicated in inflammatory bowel disease. IL-23 interacts with both the innate and adaptive immune systems, and IL-23/Th17 appears to be involved in the development of chronic intestinal inflammation. The IL-23/Th17 axis may be a critical driver of this chronic inflammation. This review summarizes the main aspects of IL-23's biological function, cytokines that control cytokine production, effectors of the IL-23 response, and the molecular mechanisms associated with IBD pathogenesis. Although IL-23 modulates and impacts the development, course, and recurrence of the inflammatory response, the etiology and pathophysiology of IBD are not completely understood, but mechanism research shows huge potential for clinical applications as therapeutic targets in IBD treatment.

Revisiting the pathogenesis of dermatophytosis: A cross-sectional analytic study of serum levels of interleukins-2, 8, 10 and 17.

Given the current epidemic-like scenario of dermatophyte infections, it is prudent to revisit the immunopathogenesis of dermatophytosis. Comprehending the intricate interactions among interleukins can aid in understanding the recent trends in infection. There is a paucity of literature on the various cytokine levels observed in the serum of patients suffering from various dermatophytoses. To study serum cytokine levels of interleukins 2, 8, 10 and 17 in patients with dermatophytosis. A cross-sectional analytic study was conducted on 64 cases of clinical dermatophyte infections (KOH confirmed) and 64 controls. The clinico-epidemiological profile of the cases was studied. By using a solid phase sandwich ELISA (enzyme-linked immunosorbent assay), the serum levels of interleukins 2, 8, 10 and 17 were measured and compared between cases and controls. Serum interleukin-2, 8, 10 and 17 levels were studied among cases based on mode of onset, duration of illness, treatment history, site of infection and multiple other morphological characteristics of the infection. The cases had statistically higher levels of interleukins-8, 10 and 17 in comparison with controls. The levels of interleukin-8 were significantly lower (p < .05) among those who had received oral antifungals. In cases where the lesion had scaling, the serum levels of interleukin-10 were significantly higher (p < .05). The lesional hyperpigmentation was significantly (p < .05) associated with low levels of interleukin-17. Also, interleukin-17 was significantly (p < .05) elevated in patients with lesions in the abdomen. It is the first time that serum interleukin levels are studied in dermatophytosis. There is an immunological dysfunction specific to dermatophytoses initiated by their infection. Key factor in this dysfunction is the elevation of IL-10, contributing to persistent infection. In turn, causing an increase in IL-17, promoting inflammation and tissue damage. This cycle of elevated IL-10 and IL-17 can further exacerbate the infection and lead to chronicity. The activity of IL-2 and the Th1 immune pathway is reduced by two opposing immune pathways: the Th17 and Th2 axes.