Interleukin-17A (IL-17A) is involved in antibody specificity to conformational epitopes.

The specificity of antibodies (Ab) is essential for the precise recognition of foreign or dangerous molecules. We have shown that mice infected with non-pathogenic Lactate Dehydrogenase Elevating Virus (LDV) inoculated with human growth hormone (hGH) or Ovalbumin (OVA), exhibit modified specificity of anti-hGH or anti-OVA Ab associated with the secretion of IFN-γ, IL-13, and IL-17. Cytokines are directly or indirectly involved in the isotypes, specificity, and affinity of Ab.

Lactate Dehydrogenase-Elevating Virus Infection Inhibits MOG Peptide Presentation by CD11b+CD11c+ Dendritic Cells in a Mouse Model of Multiple Sclerosis.

Infections may affect the course of autoimmune inflammatory diseases of the central nervous system (CNS), such as multiple sclerosis (MS). Infections with lactate dehydrogenase-elevating virus (LDV) protected mice from developing experimental autoimmune encephalomyelitis (EAE), a mouse counterpart of MS. Uninfected C57BL/6 mice immunized with the myelin oligodendrocyte glycoprotein peptide (MOG35-55) experienced paralysis and lost weight at a greater rate than mice who had previously been infected with LDV.

NLRP6 controls pulmonary inflammation from cigarette smoke in a gut microbiota-dependent manner.

Chronic obstructive pulmonary disease (COPD) is a major health issue primarily caused by cigarette smoke (CS) and characterized by breathlessness and repeated airway inflammation. NLRP6 is a cytosolic innate receptor controlling intestinal inflammation and orchestrating the colonic host-microbial interface. However, its roles in the lungs remain largely unexplored.

Cytokine Kinetics during Progression of COVID-19 in Rwanda Patients: Could IL-9/IFNγ Ratio Predict Disease Severity?

For effective treatments and preventive measures against severe COVID-19, it is essential to determine early markers of disease severity in different populations. We analysed the cytokine kinetics of 129 COVID-19 patients with mild symptoms, 68 severe cases, and 20 healthy controls for the first time in Rwanda. Pro-inflammatory (IFNγ, IL-6, TNFα), Treg (IL-10, TGFβ1, TGFβ3), Th9 (IL-9), Th17 (IL-17), and Th2 (IL-4, IL-13) cytokines, total IgM and IgG, as well as gene expressions of , and were measured at day 1, day 7, day 14, day 21, and day 28 post-infection.

Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma.

Loss of function of the von Hippel-Lindau (VHL) tumor suppressor gene is a hallmark of clear cell renal cell carcinoma (ccRCC). The importance of heterogeneity in the loss of this tumor suppressor has been under reported. To study the impact of intratumoral VHL heterogeneity observed in human ccRCC, we engineered VHL gene deletion in four RCC models, including a new primary tumor cell line derived from an aggressive metastatic case.

Inhibition of IL-12 heterodimers impairs TLR9-mediated prevention of early mouse plasmacytoma cell growth.

Introduction: Natural prevention of cancer development depends on an efficient immunosurveillance that may be modulated by environmental factors, including infections. Innate lymphoid cytotoxic cells have been shown to play a major role in this immunosurveillance. Interleukin-12 (IL-12) has been suggested to be a key factor in the activation of innate cytotoxic cells after infection, leading to the enhancement of cancer immunosurveillance.

Integrated Analysis of Cytokine Profiles in Malaria Patients Discloses Selective Upregulation of TGF-β1, β3, and IL-9 in Mild Clinical Presentation.

The proper control of Plasmodium infection requires a finely balanced immune response. Here, we evaluated the implication of TGF-β1 and TGF-β3 in this process using novel monoclonal antibodies to measure their plasma concentrations in comparison with other cytokines and the expression of FOXP3 mRNA. Plasma cytokine levels were measured in 80 patients with severe anaemic malaria and 186 with a mild presentation using ELISA, and rtPCR was used to measure FOXP3 mRNA expression.

Isoform specific anti-TGFβ therapy enhances antitumor efficacy in mouse models of cancer.

TGFβ is a potential target in cancer treatment due to its dual role in tumorigenesis and homeostasis. However, the expression of TGFβ and its inhibition within the tumor microenvironment has mainly been investigated in stroma-heavy tumors. Using B16 mouse melanoma and CT26 colon carcinoma as models of stroma-poor tumors, we demonstrate that myeloid/dendritic cells are the main sources of TGFβ1 and TGFβ3.

Novel antibodies that selectively block mouse IL-12 enable the re-evaluation of the role of IL-12 in immune protection and pathology.

The dimeric cytokine IL-12 is important in the control of various infections but also contributes to the pathology of certain diseases making it a potential target for therapy. However, its specific inhibition with antibodies is complicated by the fact that its two subunits are present in other cytokines: p40 in IL-23 and p35 in IL-35. This has led to erroneous conclusions like the alleged implication of IL-12 in experimental autoimmune encephalomyelitis (EAE).

TGFβ1 neutralization displays therapeutic efficacy through both an immunomodulatory and a non-immune tumor-intrinsic mechanism.

Background: Transforming growth factor-β (TGFβ) is emerging as a promising target for cancer therapy, given its ability to promote progression of advanced tumors and to suppress anti-tumor immune responses. However, TGFβ also plays multiple roles in normal tissues, particularly during organogenesis, raising toxicity concerns about TGFβ blockade. Dose-limiting cardiovascular toxicity was observed, possibly due to the blockade of all three TGFβ isoforms.

Lactate dehydrogenase-elevating virus enhances natural killer cell-mediated immunosurveillance of mouse mesothelioma development.

Background: Viral infections can reduce early cancer development through enhancement of cancer immunosurveillance. This study was performed to analyse this effect of viral infection in a mouse model of solid tumor.

Methods: The experimental model used was the effect of BALB/c mouse infection by lactate dehydrogenase-elevating virus on AB1 mesothelioma cancer development.

Ozone-Induced Aryl Hydrocarbon Receptor Activation Controls Lung Inflammation via Interleukin-22 Modulation.

Airborne ozone exposure causes severe lung injury and inflammation. The aryl hydrocarbon Receptor (AhR) (1), activated in pollutant-induced inflammation, is critical for cytokine production, especially IL-22 and IL-17A. The role of AhR in ozone-induced lung inflammation is unknown.

Preclinical evaluation of topically-administered PEGylated Fab' lung toxicity.

PEGylation is a promising approach to increase the residence time of antibody fragments in the lungs and sustain their therapeutic effects. However, concerns arise as to the potential pulmonary toxicity of antibody fragments conjugated to high molecular weight (HMW) polyethylene glycol (PEG), notably after repeated administrations, and the possibility of PEG accumulation in the lungs. The purpose of this proof-of-concept study is to give insights about the safety of lung administration of a Fab' anti-IL17A antibody fragment conjugated to two-armed 40 kDa PEG (PEG40).

Prophylactic treatment against GM-CSF, but not IL-17, abolishes relapses in a chronic murine model of multiple sclerosis.

The pathogenic role of IL-17 and GM-CSF has been unravelled in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). However, in most models, EAE is characterised by a monophasic attack which is not representative of the relapsing nature nor the chronicity displayed in MS. Here, we used proteolipid protein peptide (PLP ) to trigger EAE-relapses (EAE-II) in SJL mice that had recovered from a primary-EAE episode (EAE-I).

The TLR7 ligand R848 prevents mouse graft--host disease and cooperates with anti-interleukin-27 antibody for maximal protection and regulatory T-cell upregulation.

In spite of considerable therapeutic progress, acute graft--host disease still limits allogeneic hematopoietic cell transplantation. We recently reported that mouse infection with nidovirus lactate dehydrogenase elevating virus impairs disease in non-conditioned B6D2F1 recipients of parental B6 spleen cells. As this virus activates TLR7, we tested a pharmacological TLR7 ligand, R848, in this model and observed complete survival if donor and recipients were treated before transplantation.

Effects of interleukin 17A (IL-17A) neutralization on murine hepatitis virus (MHV-A59) infection.

Mice infected with mouse hepatitis virus A59 (MHV-A59) develop hepatitis and autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH), a fact closely related to the release of alarmins such as uric acid and/or high-mobility group box protein 1 (HMGB1). We studied the effect of neutralizing monoclonal antibodies (MAb) against IL-17A in our model of mouse MHV-A59-infection. MAb anti-IL-17F and anti-IFNγ were used to complement the study.

Neutralization of either IL-17A or IL-17F is sufficient to inhibit house dust mite induced allergic asthma in mice.

T helper (Th)17 immune response participates in allergic lung inflammation and asthma is reduced in the absence of interleukin (IL)-17 in mice. Since IL-17A and IL-17F are induced and bind the shared receptor IL-17RA, we asked whether both IL-17A and IL-17F contribute to house dust mite (HDM) induced asthma. We report that allergic lung inflammation is attenuated in absence of either IL-17A or IL-17F with reduced airway hyperreactivity, eosinophilic inflammation, goblet cell hyperplasia, cytokine and chemokine production as found in absence of IL-17RA.

Mouse nidovirus LDV infection alleviates graft versus host disease and induces type I IFN-dependent inhibition of dendritic cells and allo-responsive T cells.

Introduction: Viruses have developed multiple mechanisms to alter immune reactions. In 1969, it was reported that lactate dehydrogenase-elevating virus (LDV), a single stranded positive sense mouse nidovirus, delays skin allograft rejection and inhibits spleen alterations in graft versus host disease (GVHD). As the underlying mechanisms have remained unresolved and given the need for new therapies of this disease, we reassessed the effects of the virus on GVHD and tried to uncover its mode of action.

Blockade of interleukin-27 signaling reduces GVHD in mice by augmenting Treg reconstitution and stabilizing Foxp3 expression.

Reestablishment of competent regulatory pathways has emerged as a strategy to reduce the severity of graft-versus-host disease (GVHD), and recalibrate the effector and regulatory arms of the immune system. However, clinically feasible, cost-effective strategies that do not require extensive ex vivo cellular manipulation have remained elusive. In the current study, we demonstrate that inhibition of the interleukin-27p28 (IL-27p28) signaling pathway through antibody blockade or genetic ablation prevented lethal GVHD in multiple murine transplant models.

Structure and Expression of Different Serum Amyloid A (SAA) Variants and their Concentration-Dependent Functions During Host Insults.

Serum amyloid A (SAA) is, like C-reactive protein (CRP), an acute phase protein and can be used as a diagnostic, prognostic or therapy follow-up marker for many diseases. Increases in serum levels of SAA are triggered by physical insults to the host, including infection, trauma, inflammatory reactions and cancer. The order of magnitude of increase in SAA levels varies considerably, from a 10- to 100- fold during limited inflammatory events to a 1000-fold increase during severe bacterial infections and acute exacerbations of chronic inflammatory diseases.

The cytokine-serum amyloid A-chemokine network.

Levels of serum amyloid A (SAA), a major acute phase protein in humans, are increased up to 1000-fold upon infection, trauma, cancer or other inflammatory events. However, the exact role of SAA in host defense is yet not fully understood. Several pro- and anti-inflammatory properties have been ascribed to SAA.

Novel highly specific anti-periostin antibodies uncover the functional importance of the fascilin 1-1 domain and highlight preferential expression of periostin in aggressive breast cancer.

Periostin (POSTN), a secreted homodimeric protein that binds integrins αvβ3, αvβ5, and α6β4, was originally found to be expressed in fetal tissues and in the adult upon injury particularly bone fractures due to its role in remodelling and repair. Recently it was found to be over-expressed in human breast cancer and a variety of other tumour types including head and neck squamous cell carcinoma, where its overexpression correlates with increased tumour invasion. Progress in studying its functional role in tumour pathogenesis has been hampered by the paucity of antibodies for its specific and sensitive detection.