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Thymic stromal lymphopoietin (TSLP) acts as a potent mucosal adjuvant for HIV-1 gp140 vaccination in mice.

The development of a successful vaccine against HIV is likely to require the induction of strong and long-lasting humoral immune responses a … (CT). The use of TSLP as an adjuvant skewed both the cellular and humoral immune responses towards Th2 cells. This is the first time that TSLP has been demonstrated to have a positive effect as a mucosal adjuvant, and specifically to promote mucosal and systemic responses to HIV gp140.

MyD88 negatively controls hypergammaglobulinemia with autoantibody production during bacterial infection.

A large body of evidence has convincingly shown that Toll-like receptors are necessary sensors for infections with pathogens, but their activation was also suggested to generate autoimmunity. During experimental infections, the lack of these sensors or of their signaling molecules should lead to a deficient immune response. We found out that MyD88, the major adaptor of the Toll/interleukin-1 (Toll/IL-1) receptor signaling pathway, can actually act as a negative regulator of B-cell function in some settings. MyD88-deficient mice infected by Borrelia burgdorferi developed extreme hypergammaglobu

Нейроинфламмация в нейродегенеративных заболеваниях: сосредоточение внимания на посредничестве лимфоцитов T.

Нейродегенеративные заболевания представляют собой группу заболеваний, характеризующихся постепенным ухудшением центральной нервной системы, что приводит к снижению когнитивных, моторных и эмоциональных способностей пациентов. Нейроинфламмация играет важную роль в развитии этих заболеваний. Вместе с тем исследования терапевтических подходов к целенаправленной борьбе с нейроинфламмацией носят ограниченный характер. Все шире признается роль лимфоцитов, которые являются важнейшими посредниками адаптивной иммунной реакции, в нейродегенеративных заболеваниях. В настоящем обзоре основное внимание уд

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… Caza and Landas (2015) summarized the subsets of CD4 + T cells as including Th1 cells, Th2 cells, Th9 cells, Th17 cells, Th22 cells, Th15 cells, and Tregs. In NDD, Th1 cells, Th2 cells, Th17 cells, and Tregs play significant roles in neuroinflammation. … Activated Th2 cells secrete various cytokines, including IL-4, IL-9, and IL-10. The IL-4 and IL-13 produced by Th2 cells typically exert anti-inflammatory effects by inhibiting the proliferation of Th1 cells. …

The development and maintenance of immunity against visceral leishmaniasis.

Understanding the development and maintenance of immunological memory is important for efforts to eliminate parasitic diseases like leishman … or resident parasites, while other Th cell subset, including FoxP3+ natural regulatory T cells and Th2 cells can promote disease progression by suppressing the activities of Th1 cells. Upon resolution of a primary Leishmania infection, different subsets of CD4+ T cells, including tissue-resident memory T cells, effector memory T cells, central memory T cel …

Therapeutic targeting with DABIL-4 depletes myeloid suppressor cells in 4T1 triple-negative breast cancer model.

In many solid tumors including triple-negative breast cancer (TNBC), upregulation of the interleukin-4 receptor (IL-4R) has been shown to promote cancer cell proliferation, apoptotic resistance, metastatic potential, and a Th2 response in the tumor microenvironment (TME). Since immunosuppressive cells in the TME and spleen including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) also express the IL-4R, we hypothesized that selective depletion of IL-4R-bearing cells in TNBC would result in the direct killing of tumor cells and the depletion of immunosuppressive

Unique B- and plasma cell signature differentiates hidradenitis suppurativa from psoriasis and atopic dermatitis.

INTRODUCTION: Hidradenitis suppurativa (HS), psoriasis (PsO), and atopic dermatitis (AD) have unique disease pathogenesis and distinct pathology, despite sharing some immunological pathways. This study aimed to evaluate the transcriptomic differences between HS, PsO, and AD lesions, which drive these unique pathogenic features. METHODS: Bulk RNA sequencing was performed on 19 healthy controls (HC), 15 HS, 21 PsO, and 15 AD lesional skin samples. RESULTS: PsO lesions were defined by a strong interleukin (IL)-17 signature, and AD lesions had increased T helper (Th2) signaling. HS lesions had a

Stem-like CD4 T cells in tumors: an emerging framework for antitumor immunity.

Recent studies have identified antigen-experienced TCF1+PD-1+ lineage-negative (lin-) CD4 T cells in several tumor types. Strictly, stemness requires durable self-renewal and multipotent output demonstrated at the single-cell level; these criteria have not yet been established for an individual tumor-associated CD4 T cell. Operationally, this review uses "stem-like CD4 T cells" for TCF1+PD-1+ lin- populations that lack canonical terminal TH1, TH2, TH17, and Treg commitment programs and show population-level persistence and multilineage output. Pending single-cell lineage tracing, these populat

Altered Immune Profiles in Non-Failing Heart Donors With Induced Long QT Syndrome: A Potential Risk Factor for Cardiac Allograft Vasculopathy.

INTRODUCTION: Cardiac allograft vasculopathy (CAV) develops more aggressively in recipients of hearts from brain-dead (BD) donors with induced long QT syndrome (iLQTS), yet the underlying mechanisms remain poorly understood. In this study, we employ a multi-omics and experimental framework to explore the role of neuro-immune interactions in non-failing donor hearts affected by iLQTS. METHODS: Single-nuclei RNA sequencing (snRNA-seq) compared four iLQTS and four non-arrhythmic non-failing donor hearts. Pathway enrichment and cell-cell communication were assessed. Plasma proteome data from BD d

Interleukin-31 in Respiratory Type 2 Inflammatory Diseases: Mechanistic Insights and Therapeutic Potential.

Respiratory type 2 inflammatory diseases, including asthma and allergic rhinitis (AR), and chronic rhinosinusitis with nasal polyps (CRSwNP), are characterized by epithelial dysfunction, immune dysregulation, and chronic airway inflammation. Interleukin-31 (IL-31), primarily produced by Th2 cells and other immune and structural cells, has emerged as a pivotal mediator in these conditions. By activating the JAK/STAT and MAPK signaling, IL-31 drives chemokine release, eosinophil recruitment, mucus hypersecretion, and neuroimmune responses. Clinical studies demonstrate that IL-31 levels are eleva…

A preclinical model of peripheral T-cell lymphoma GATA3 reveals DNA damage response pathway vulnerability.

Peripheral T-cell lymphoma (PTCL) represents a rare group of heterogeneous diseases in urgent need of effective treatments. A scarcity of disease-relevant preclinical models hinders research advances. Here, we isolated a novel mouse (m)PTCL by serially transplanting a lymphoma from a germinal center B-cell hyperplasia model (Cγ1-Cre Blimp1fl/fl ) through immune-competent mice. Lymphoma cells were identified as clonal TCRβ+ T-helper cells expressing T-follicular helper markers. We also observed coincident B-cell activation and development of a de novo B-cell lymphoma in the model, reminiscent o

The Role of Vitamin D in COVID-19 and the Impact of Pandemic Restrictions on Vitamin D Blood Content.

Vitamin D is a hormone regulating the immune system and playing a pivotal role in responses to microbial infections. It regulates inflammatory processes by influencing the transcription of immune-response genes in macrophages, T cells, and dendritic cells. The proven role of vitamin D in many infectious diseases of the respiratory tract indicated that vitamin D should also play a role in SARS-CoV-2 infection. Vitamin D inhibits cytokine storm by switching the pro-inflammatory Th1 and Th17 to the anti-inflammatory Th2 and Treg response. Vitamin D is therefore expected to play a role in preventi

Humoral and cellular immune responses to CoronaVac up to one year after vaccination.

Coronavac is a widely used SARS-CoV-2 inactivated vaccine, but its long-term immune response assessment is still lacking. We evaluated SARS-CoV-2-specific immune responses, including T cell activation markers, antigen-specific cytokine production and antibody response following vaccination in 53 adult and elderly individuals participating in a phase 3 clinical trial. Activated follicular helper T (Tfh), non-Tfh and memory CD4+ T cells were detected in almost all subjects early after the first vaccine dose. Activated memory CD4+ T cells were predominantly of central and effector memory T cell p

Atopic Neutrophils Prevent Postviral Airway Disease.

Respiratory syncytial virus (RSV) infection in infancy is associated with increased risk of asthma, except in those with allergic disease at the time of infection. Using house dust mite allergen, we examined the effect of pre-existing atopy on postviral airway disease using Sendai virus in mice, which models RSV infection in humans. Sendai virus drives postviral airway disease in nonatopic mice; however, pre-existing atopy protected against the development of airway disease. This protection depended upon neutrophils, as depletion of neutrophils at the time of infection restored the susceptibil

Effect of Ancylostoma ceylanicum hookworm platelet inhibitor on platelet adhesion and peripheral blood mononuclear cell proliferation.

Ancylostoma ceylanicum is a zoonotic parasitic nematode that can cause iron-deficiency anemia and malnutrition in humans. A. ceylanicum hookworm platelet inhibitor (Ace-HPI) can inhibit platelet aggregation in the host to facilitate blood sucking, but whether it possesses platelet adhesion inhibitory activity or immunomodulatory role is yet unknown. To explore the effect of Ace-HPI on platelet adhesion, we expressed the recombinant protein in two competent cells, BL21 (DE3) and Rosetta-gami2 (DE3), and incubated this protein with canine platelets in a 96-well microplate. Ace-HPI was used to st

Biogenic silver nanoparticles reduce adherence, infection, and proliferation of toxoplasma gondii RH strain in HeLa cells without inflammatory mediators induction.

The highlights of biogenic silver nanoparticles (AgNp-Bio) include low toxicity - depending on size and concentration - and efficient antiparasitic activity. Therefore, the objective of this study was to assess the action of the AgNp-Bio on HeLa cells in an infection with strain of RH Toxoplasma gondii. Firstly, we performed a cellular viability test and characterized the AgNp-Bio to proceed with the infection of HeLa cells with T. gondii to be treated using AgNp-Bio or conventional drugs. Subsequently, we determined the level of standard cytokines Th1/Th2 as well as the content of nitric oxid

Immunization With Mycobacterium tuberculosis Antigens Encapsulated in Phosphatidylserine Liposomes Improves Protection Afforded by BCG.

Liposomes have been long considered as a vaccine delivery system but this technology remains to be fully utilized. Here, we describe a novel liposome-based subunit vaccine formulation for tuberculosis (TB) based on phosphatidylserine encapsulating two prominent TB antigens, Ag85B, and ESAT-6. We show that the resulting liposomes (Lipo-AE) are stable upon storage and can be readily taken up by antigen presenting cells and that their antigenic cargo is delivered and processed within endosomal cell compartments. The Lipo-AE vaccine formulation combined with the PolyIC adjuvant induced a mixed Th1

The Equivocal Role of Th17 Cells and Neutrophils on Immunopathogenesis of Leishmaniasis.

Advances in the understanding of leishmaniasis progression indicate that cellular interactions more complex than the Th1/Th2 paradigm define the course of infection. Th17 cells are a crucial modulator of adaptive immunity against Leishmania parasites acting mainly on neutrophil recruitment and playing a dual role at the site of infection. This review describes the roles of both these cell types in linking innate defense responses to the establishment of specific immunity. We focus on the Th17-neutrophil interaction as a crucial component of anti-Leishmania immunity, and the clinical evolution

IL-37 and leprosy: A novel cytokine involved in the host response to Mycobacterium leprae infection.

Leprosy is a chronic infectious granulomatous disease caused by Mycobacterium leprae, in which the clinical outcome depends on the pattern of the host immune response. Because it is a spectral disease, leprosy is a good model for studying the immunology of the pathogen-host relationship. Although previous studies have characterized the participation of cytokine profiles such as Th1, Th2, Th7, Treg, Th9, and Th22 responses in leprosy, the role of new cytokines such as IL-37 have not yet been described for the spectral model of the disease. Here, we used an immunohistochemical technique to evalu

The Helminth-Derived Immunomodulator AvCystatin Reduces Virus Enhanced Inflammation by Induction of Regulatory IL-10+ T Cells.

Respiratory Syncytial Virus (RSV) is a major pathogen causing low respiratory tract disease (bronchiolitis), primarily in infants. Helminthic infections may alter host immune responses to both helminths and to unrelated immune triggers. For example, we have previously shown that filarial cystatin (AvCystatin/Av17) ameliorates allergic airway inflammation. However, helminthic immunomodulators have so far not been tested in virus-induced disease. We now report that AvCystatin prevents Th2-based immunopathology in vaccine-enhanced RSV lung inflammation, a murine model for bronchiolitis. AvCystati

The effect of omalizumab on eosinophilic inflammation of the respiratory tract in patients with allergic asthma.

Bronchial asthma is characterised by high levels of immunoglobulin E (IgE) and overproduction of pro-inflammatory cytokines, including interleukins IL-4, IL-13 and IL-5 needed for, amongst other things, the production of IgE and the differentiation, maturation, migration and survival of eosinophils. Eosinophils are one of the most important cells in allergic inflammation. Their presence in tissue is linked to the persistence of inflammatory infiltrate, tissue damage and remodelling. Although these cells are very sensitive to corticosteroids, some asthmatic patients do not respond to high doses