Granulocytes and mast cells in AllergoOncology-Bridging allergy to cancer: An EAACI position paper.

Derived from the myeloid lineage, granulocytes, including basophils, eosinophils, and neutrophils, along with mast cells, play important, often disparate, roles across the allergic disease spectrum. While these cells and their mediators are commonly associated with allergic inflammation, they also exhibit several functions either promoting or restricting tumor growth. In this Position Paper we discuss common granulocyte and mast cell features relating to immunomodulatory functions in allergy and in cancer.

Mould allergen Alt a 1 spiked with the micronutrient retinoic acid reduces Th2 response and ameliorates Alternaria allergy in BALB/c mice.

Background: We investigated the biological function of the mould allergen Alt a 1 as a carrier of micronutrients, such as the vitamin A metabolite retinoic acid (RA) and the influence of RA binding on its allergenicity in vitro and in vivo.

Methods: Alt a 1-RA complex formation was analyzed in silico and in vitro. PBMCs from Alternaria-allergic donors were stimulated with Alt a 1 complexed with RA (holo-Alt a 1) or empty apo-Alt a 1 and analyzed for cytokine production and CD marker expression.

AllergoOncology: Biomarkers and refined classification for research in the allergy and glioma nexus-A joint EAACI-EANO position paper.

Epidemiological studies have explored the relationship between allergic diseases and cancer risk or prognosis in AllergoOncology. Some studies suggest an inverse association, but uncertainties remain, including in IgE-mediated diseases and glioma. Allergic disease stems from a Th2-biased immune response to allergens in predisposed atopic individuals.

Nutritional Provision of Iron Complexes by the Major Allergen Alt a 1 to Human Immune Cells Decreases Its Presentation.

is a common fungus strongly related with severe allergic asthma, with 80% of affected individuals being sensitized solely to its major allergen Alt a 1. Here, we assessed the function of Alt a 1 as an innate defense protein binding to micronutrients, such as iron-quercetin complexes (FeQ2), and its impact on antigen presentation in vitro. Binding of Alt a 1 to FeQ2 was determined in docking calculations.

Ameliorating Atopy by Compensating Micronutritional Deficiencies in Immune Cells: A Double-Blind Placebo-Controlled Pilot Study.

Background: Functional iron deficiency facilitates allergy development and amplifies the symptom burden in people experiencing allergies. Previously we selectively delivered micronutrients to immune cells with β-lactoglobulin as carrier (holoBLG), resulting in immune resilience and allergy prevention.

Objective: The clinical efficacy of a food for special medical purposes-lozenge containing β-lactoglobulin with iron, polyphenols, retinoic acid, and zinc (holoBLG lozenge) was assessed in allergic women.

Secretory protein beta-lactoglobulin in cattle stable dust may contribute to the allergy-protective farm effect.

Background: Growing up on a cattle farm and consuming raw cow's milk protects against asthma and allergies. We expect a cattle-specific protein as active component in this farm effect.

Methods: Dust was collected from cattle and poultry stables and from mattresses of households.

AllergoOncology: Danger signals in allergology and oncology: A European Academy of Allergy and Clinical Immunology (EAACI) Position Paper.

The immune system interacts with many nominal 'danger' signals, endogenous danger-associated (DAMP), exogenous pathogen (PAMP) and allergen (AAMP)-associated molecular patterns. The immune context under which these are received can promote or prevent immune activating or inflammatory mechanisms and may orchestrate diverse immune responses in allergy and cancer. Each can act either by favouring a respective pathology or by supporting the immune response to confer protective effects, depending on acuity or chronicity.

Micronutritional supplementation with a holoBLG-based FSMP (food for special medical purposes)-lozenge alleviates allergic symptoms in BALB/c mice: Imitating the protective farm effect.

Background: Previously, the protective farm effect was imitated using the whey protein beta-lactoglobulin (BLG) that is spiked with iron-flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for special medical purposes (FSMP) using catechin-iron complexes as ligands for BLG. The lozenge was tested in vitro and in a therapeutical BALB/c mice model.

IgG4 induces tolerogenic M2-like macrophages and correlates with disease progression in colon cancer.

IgG4 subclass antibodies are expressed in alternative Th2 environments featuring high IL-10 expression, including several solid tumors such as melanoma. To induce tolerance, allergen immunotherapy mediates antibody class switching from pro-inflammatory IgE to anti-inflammatory IgG4. We previously reported that IgG4 drives allergic M2 macrophages toward tolerogenic states.

Filling the Antibody Pipeline in Allergy: PIPE Cloning of IgE, IgG and IgG against the Major Birch Pollen Allergen Bet v 1.

Birch pollen allergy is among the most prevalent pollen allergies in Northern and Central Europe. This IgE-mediated disease can be treated with allergen immunotherapy (AIT), which typically gives rise to IgG antibodies inducing tolerance. Although the main mechanisms of allergen immunotherapy (AIT) are known, questions regarding possible Fc-mediated effects of IgG antibodies remain unanswered.

Galanin is a potent modulator of cytokine and chemokine expression in human macrophages.

The regulatory peptide galanin is broadly distributed in the central- and peripheral nervous systems as well as in non-neuronal tissues, where it exerts its diverse physiological functions via three G-protein-coupled receptors (GAL-R). Regulatory peptides are important mediators of the cross-communication between the nervous- and immune systems and have emerged as a focus of new therapeutics for a variety of inflammatory diseases. Studies on inflammatory animal models and immune cells revealed both pro- and anti-inflammatory functions of galanin.

IgE re-programs alternatively-activated human macrophages towards pro-inflammatory anti-tumoural states.

Background: Antibody Fc-driven engagement of macrophages is critical for evoking cellular activation and effector functions and influencing tumour-associated macrophage (TAM) recruitment. We previously reported that IgE class antibodies promote restriction of cancer growth in rodent models associated with significant TAM infiltration. However, the human macrophage-associated IgE-Fc Receptor (FcεR) axis remains unexplored.

AllergoOncology: Microbiota in allergy and cancer-A European Academy for Allergy and Clinical Immunology position paper.

The microbiota can play important roles in the development of human immunity and the establishment of immune homeostasis. Lifestyle factors including diet, hygiene, and exposure to viruses or bacteria, and medical interventions with antibiotics or anti-ulcer medications, regulate phylogenetic variability and the quality of cross talk between innate and adaptive immune cells via mucosal and skin epithelia. More recently, microbiota and their composition have been linked to protective effects for health.

Comparing biologicals and small molecule drug therapies for chronic respiratory diseases: An EAACI Taskforce on Immunopharmacology position paper.

Chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), together with their comorbidities, bear a significant burden on public health. Increased appreciation of molecular networks underlying inflammatory airway disease needs to be translated into new therapies for distinct phenotypes not controlled by current treatment regimens. On the other hand, development of new safe and effective therapies for such respiratory diseases is an arduous and expensive process.

IgG4 drives M2a macrophages to a regulatory M2b-like phenotype: potential implication in immune tolerance.

Background: Macrophages can be converted in vitro into immunoregulatory M2b macrophages in the presence of immune complexes (ICs), but the role of the specific subclasses IgG1 or IgG4 in this phenotypic and functional change is not known.

Objective: We aimed to refine the original method by applying precisely defined ICs of the subclasses IgG4 or IgG1 constructed by two independent methods.

Methods: Monocyte-derived macrophages (MDMs) were treated with M-CSF, followed by IL-4/IL-13 to induce the M2a allergic phenotype.

Bidirectional Regulation of COX-2 Expression Between Cancer Cells and Macrophages.

Background/aim: Our aim was to investigate the crosstalk between tumor and immune cells (M2 macrophages) and its effects on cyclo-oxygenase-2 (COX2) regulation in canine mammary tumors (CMT).

Materials And Methods: Sh1b CMT cells and human BT474 mammary or HT29 colon cancer cells were co-cultured with canine peripheral blood mononuclear cells (PBMCs) or with macrophage-like differentiated THP1 monocytes (dTHP1). Intracellular COX2 expression by PBMCs, dTHP1 and cancer cells was evaluated by flow cytometry.

Retinoic acid prevents immunogenicity of milk lipocalin Bos d 5 through binding to its immunodominant T-cell epitope.

The major cow's milk allergen Bos d 5 belongs to the lipocalin protein family, with an intramolecular pocket for hydrophobic ligands. We investigated whether Bos d 5 when loaded with the active vitamin A metabolite retinoic acid (RA), would elicit differential immune responses compared to the unloaded state. By in silico docking an affinity energy of -7.

Canine macrophages can like human macrophages be in vitro activated toward the M2a subtype relevant in allergy.

The M2a subtype of macrophages plays an important role in human immunoglobulin E (IgE-mediated allergies) and other Th2 type immune reactions. In contrast, very little is known about these cells in the dog. Here we describe an in vitro method to activate canine histiocytic DH82 cells and primary canine monocyte-derived macrophages (MDMs) toward the M2a macrophages using human cytokines.

Linking iron-deficiency with allergy: role of molecular allergens and the microbiome.

Atopic individuals tend to develop a Th2 dominant immune response, resulting in hyperresponsiveness to harmless antigens, termed allergens. In the last decade, epidemiological studies have emerged that connected allergy with a deficient iron-status. Immune activation under iron-deficient conditions results in the expansion of Th2-, but not Th1 cells, can induce class-switching in B-cells and hampers the proper activation of M2, but not M1 macrophages.

The Proinflammatory Cytokine GITRL Contributes to TRAIL-mediated Neurotoxicity in the HCN-2 Human Neuronal Cell Line.

Background: Cytokines belonging to the TNF superfamily play a relevant role in neurodegenerative processes. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), released during neuronal injury, has proven to potently mediate and sustain neurotoxic processes leading to neuronal death. Similarly to TRAIL, the cytokine Glucocorticoid-induced TNF receptor ligand (GITRL) is able to transduce proapoptotic signals.

A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs.

Infiltrating cells of the immune system are widely accepted to be generic constituents of tumor microenvironment. It has been well established that the development of mammary cancer, both in humans and in dogs, is associated with alterations in numbers and functions of immune cells at the sites of tumor progression. These tumor infiltrating immune cells seem to exhibit exclusive phenotypic and functional characteristics and mammary cancer cells can take advantage of signaling molecules released by them.