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Interleukin 21 as a new possible player in pemphigus: Is it a suitable target?

Pemphigus is a rare autoimmune disease, which could be fatal without treatment. Recently, target therapy is increasingly being used in different autoimmune diseases. However, there are limited studies associated with target therapy in pemphigus. In this study, it was tried to identify the role of interleukin (IL) -21 in patients with pemphigus. Based on the available studies on the role of IL-21 associated with several cells, including T cells, B cells, natural killer (NK) cells, natural killer T (NKT) cells, mast cells as well as regulatory B cells and regulatory T cells, the possible roles o

Interleukin-21 является критически важным цитокином для формирования клеток долгоживущей плазмы с конкретным вирусом.

Долгоживущие плазменные клетки, которые живут в костном мозге, формируют антитела в отсутствие антигена и являются клеточной основой длительного юморального иммунитета. Формирование этих долгоживущих плазменных клеток зависит от ряда высокоорганизованных взаимодействий между антигенно специфическими CD4 T и B клетками, а также от формирования микробных центров (ГЦ). В этом исследовании мы изучили роль цитокина интерлейкина-21 (IL-21) в регулировании юморального иммунитета при острых вирусных инфекциях. Используя мыши IL-21-дефицит-рецептора (IL-21R(-/-)), мы обнаружили, что конкретно по вирусу

Совпадение в аннотации оригинала
Long-lived plasma cells that reside in the bone marrow constitutively produce antibody in the absence of antigen and are the cellular basis … d the formation of germinal centers (GCs). In this study, we have examined the role of the cytokine interleukin-21 (IL-21) in regulating humoral immunity during acute viral infections. Using IL-21 receptor-deficient (IL-21R(-/-)) mice, we found that virus-specific CD4 T cells were generated after infection with lymphocytic choriomeningitis virus (LCMV) and that …

Interleukin-21 Regulates Natural Killer Cell Responses During Mycobacterium tuberculosis Infection.

BACKGROUND: In the current study, we determined the effects of interleukin (IL)-21 on human natural killer (NK) cells and monocyte responses during Mycobacterium tuberculosis (Mtb) infection. METHODS: We found that Mtb stimulated CD4+ and NK T cells from healthy individuals with latent tuberculosis infection (LTBI+) are major sources of IL-21. CD4+ cells from tuberculosis patients secreted less IL-21 than did CD4+ cells from healthy LTBI+ individuals. Interleukin-21 had no direct effect on Mtb-stimulated monocytes. RESULTS: Interleukin-21-activated NK cells produced interferon (IFN)-γ, perfo…

B-cell memory and primary immune deficiencies: interleukin-21 related defects.

PURPOSE OF REVIEW: The purpose of this study is to describe recent advances in our understanding of the role of interleukin-21 (IL-21) in B-cell maturation, and how defects in IL-21 receptor (IL-21R) signalling pathways (IL-21R/γc/JAK3/STAT3) are related to primary immune deficiencies. RECENT FINDINGS: Abnormal signalling through IL-21R/γc/JAK3/STAT3 pathway has been related to decreased specific antibody responses following vaccination, and to increased susceptibility to encapsulated bacterial infections. This is manifested in the hyper-IgE syndrome, X-linked and JAK3-related severe combined…

Impact of genetic polymorphisms in the interleukin-18 and interleukin-21 genes on the risk and clinical outcomes of multiple sclerosis.

BACKGROUND: This study was designed to investigate the association of IL-18-137G/C (rs187238) and IL-21-1472G/T (rs2055979) single nucleotide polymorphisms (SNPs) with the risk of MS, the disease progression, and related clinical features. METHODS: In this study, 271 Egyptian individuals participated, including 131 MS cases (relapsing-remitting (RR-MS) cases [N = 99], and progressive MS cases [N = 32]) and 140 unrelated healthy controls. The association between IL-18-137G/C (rs187238) and IL-21-1472G/T (rs2055979) single nucleotide polymorphisms (SNPs) and the risk of MS and the disease progr

Decreased interleukin-21 expression in skin and blood in advanced mycosis fungoides.

Interleukin (IL)-21 is regarded as a potent antitumor agent, which increases the cytotoxicity of both natural killer (NK) and CD8(+) T cells. In this study, we investigated the role of IL-21 in mycosis fungoides (MF). IL-21 mRNA expression levels in patch and plaque MF were significantly higher than those in normal skin. IL-21 mRNA expression levels in tumor MF were significantly decreased compared with those in patch and plaque MF. Interestingly, mRNA expression levels of IL-21 in MF lesional skin significantly correlated with those of T-helper type-1 cytokines/chemokines such as CXCL10, CXCL

Interleukins 18 and 21: biology, mechanisms of action, toxicity, and clinical activity.

Interleukins 18 and 21 have been described, and the effect of each upon immune response and experimental tumors in animals has been the subject of much recent work. Both interleukins have shown antitumor effects in animals, which in some models are striking for their duration, specificity, and ability to protect against rechallenge with the same tumor. These characteristics suggest immunologic involvement in the antitumor response, and several papers suggest involvement of both innate and adaptive immune mechanisms. Recent early phase I clinical trials in human cancer patients have demonstrate

Association between interleukin-21 gene polymorphisms (rs12508721) and HBV-related hepatocellular carcinoma.

Interleukin-21 (IL-21), as a multifunctional cytokine, plays an important role in many diseases, such as cancer, inflammatory and autoimmune diseases. We aimed to investigate the relationship between polymorphisms of IL-21 gene and susceptibility of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in a Chinese population. Studied subjects were divided into three groups: 100 patients with HBV-related HCC, 115 patients with chronic HBV infection and 127 healthy controls. Genomic DNA was isolated from peripheral blood, and the polymerase chain reaction-ligase detection reaction (PCR…

Evaluation of serum placenta-specific gene 8 protein, total antioxidant capacity, interleukin-10, interleukin-17A, interleukin-21 and interleukin-33 levels in Turkish women with gestational diabetes mellitus.

PURPOSE: Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that begins or is diagnosed during pregnancy. Our study aimed to establish a correlation between proinflammatory and anti-inflammatory response in order to be able to develop treatment strategies and determine early diagnosis biomarkers in the sera of cases diagnosed with GDM. Moreover, we aimed to investigate interleukin (IL), placenta-specific gene 8 protein (PLAC8) and total antioxidant capacity (TAC) in patients with GDM. METHODS: A total of 121 patients were included in the study. These were divided into

Interleukin 21 - its potential role in the therapy of B-cell lymphomas.

Interleukin-21 (IL-21), a member of IL-2 cytokine family, has pleotropic biological effects on lymphoid and myeloid cells. During the past 15 years, since the discovery of IL-21, great advances have been made regarding its biological activity and the mechanisms controlling IL-21-mediated cellular responses, especially in hematological malignancies. Preclinical studies have shown that IL-21R is expressed on healthy and neoplastic B-cells and exogenous IL-21 can induce direct apoptosis of IL-21R expressing B-cell non-Hodgkin lymphomas (NHL), making it a potentially attractive anti-lymphoma thera…

Interleukin-21 knockout reduces bone loss in ovariectomized mice by inhibiting osteoclastogenesis.

Estrogen deficiency accelerates osteoporosis in elderly women. However, the role of IL-21 in postmenopausal osteoporosis remains unclear. Female wild-type (WT) C57BL/6 and IL-21 knockout (KO) mice were used for ovariectomy (OVX). Here, IL-21 levels were significantly increased in the serum and bone tissues of WT-OVX mice. The trabecular bone space of the femur was significantly increased, and the bone mass was reduced in OVX mice, accompanied by a significant decrease in the maximum load, energy absorption, and elastic modulus indices. In contrast, IL-21 knockout effectively alleviated the eff

Role of interleukin-21 isoform in dextran sulfate sodium (DSS)-induced colitis.

Interleukin-21 (IL-21) is overproduced in human intestines affected by inflammatory bowel disease (IBD) and in the gut of mice with DSS-induced colitis. IL-21-deficient mice are largely protected against DSS-induced colitis, indicating that IL-21 plays a key role in the development of IBD. We previously identified a novel IL-21 isoform named IL-21iso. In this study, we found that in addition to the conventional IL-21, IL-21iso mRNA was also expressed in the colon with DSS-induced colitis. To investigate whether IL-21iso plays a role in DSS-induced colitis, we established transgenic mice (mIL-2…

Modulation of the Interleukin-21 Pathway with Interleukin-4 Distinguishes Common Variable Immunodeficiency Patients with More Non-infectious Clinical Complications.

PURPOSE: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and clinical manifestations such as infections, autoimmunity, and malignancy. We sought to determine if responsiveness to interleukin-21 (IL-21), a key cytokine for B cell differentiation, correlates with distinct clinical phenotypes in CVID. METHODS: CVID subjects were recruited through the Canadian Primary Immunodeficiency Evaluative Survey registry. Peripheral blood mononuclear cells were cultured with anti-CD40 ± interferon-gamma, interleukin-4 (IL-4), IL-21, and/or IL-4+IL-21. B cell subpopulations…

Elevated Interleukin-21 expression is correlated with systemic sclerosis' severity in Tunisian patients.

Systemic sclerosis (SSc), a rare and lethal autoimmune disorder where patients presents diverse clinical features, therefore unravelling a potential biomarker within a specific cohort is crucial for improving patient care, especially for rare diseases. This study sought to identify potential biomarkers in Tunisian SSc patients. Gene expression analysis of interleukins (IL)-21 and IL-22 in peripheral blood mononuclear cells, using quantitative real-time polymerase chain reaction (qrt-pcr), revealed upregulated IL-21 and downregulated IL-22 in SSc patients compared to healthy controls. Notably,

Loss of interleukin-21 leads to atrophic germinal centers in multicentric Castleman's disease.

Both multicentric Castleman's disease (MCD) and immunoglobulin (Ig)G4-related disease (IgG4-RD) are systemic diseases, presenting with hypergammaglobulinemia and elevated serum levels of IgG4. However, with regard to histopathological findings, MCD shows atrophic germinal centers. On the other hand, expanded germinal centers are detected in IgG4-RD. We extracted germinal centers from specimens of each disorder by microdissection and analyzed the expression of mRNAs by real-time polymerase chain reaction to clarify the mechanisms underlying atrophied germinal centers in MCD. This analysis discl

Interleukin-21--a biomarker of importance in predicting myocardial function following acute infarction?

INTRODUCTION: Following acute myocardial infarction (AMI), the acute inflammatory response contributes to wound healing but also to progressive myocardial injury. Interleukin-21 (IL-21) plays a key role in immunoregulation; whether IL-21 is associated with left ventricular (LV) remodelling after AMI is unknown. METHODS: Plasma IL-21 concentrations were measured in 100 patients (age 58.9 ± 12.0 years, 77% male) admitted with AMI and LV dysfunction, at baseline (mean 46 h) and again at 24 weeks; cardiac magnetic resonance and measurement of B-type natriuretic peptide, monocyte chemoattractant p…

Interleukin-21 is a critical regulator of CD4 and CD8 T cell survival during priming under Interleukin-2 deprivation conditions.

Optimal T cell activation and expansion require binding of the common gamma-chain (γc) cytokine Interleukin-2 (IL-2) to its cognate receptor that in turn engages a γc/Janus tyrosine kinase (Jak)3 signaling pathway. Because of its restricted expression by antigen-activated T cells and its obligatory role in promoting their survival and proliferation, IL-2 has been considered as a selective therapeutic target for preventing T cell mediated diseases. However, in order to further explore IL-2 targeted therapy, it is critical to precisely understand its role during early events of T cell activation

Potential anti-EBV effects associated with elevated interleukin-21 levels: a case report.

BACKGROUND: Germinal center derived memory B cells and plasma cells constitute, in health and during EBV reactivation, the largest functional EBV reservoir. Hence, by reducing germinal center derived formation of memory B cells and plasma cells, EBV loads may be reduced. Animal and in-vitro models have shown that IL-21 can support memory B and plasma cell formation and thereby potentially contribute to EBV persistence. However, IL-21 also displays anti-viral effects, as mice models have shown that CD4+ T cell produced IL-21 is critical for the differentiation, function and survival of anti-vir