Rodolfo Bianchini

University of Veterinary Medicine, Vienna | vetmed · Messerli Forschungsinstitut

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 dono...

Background: We previously proposed the whey protein beta-lactoglobulin (BLG) loaded with iron-siderophore complexes as the active principle in the farm protective effect against allergies. A lozenge as food for specific medical purposes (FSMP) was formulated to assess its therapeutical efficacy in BALB/c mice and in-vitro experiments. Methods: Bind...

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 individual...

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on imm...

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 individual...

Alternaria alternata 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 presentatio...

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 allerg...

Background Functional iron deficiency facilitates allergy development and amplifies the symptom burden in allergy sufferers. Previously micronutrients were selectively delivered to immune cells with beta-lactoglobulin as carrier (holoBLG), resulting in immune resilience and allergy prevention. Objective The clinical efficacy of a FSMP (food for sp...

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. Urine was obtained from cattle, and ambient aerosols were sampled....

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

Therapeutic advances using targeted biologicals and small‐molecule drugs have achieved significant success in the treatment of chronic allergic, autoimmune, and inflammatory diseases particularly for some patients with severe, treatment‐resistant forms. This has been aided by improved identification of disease phenotypes. Despite these achievements...

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 to...

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-mediate...

Among the four immunoglobulin G (IgG) subclasses, IgG4 is the least represented in serum of a healthy human and it is considered an “odd” antibody. The IgG4 antibody has unique structural features that affect its biological function. These include the ability to undergo antigen-binding fragment (Fab)-arm exchange, to create fragment crystallizable...

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 (GAL1-3-R). Regulatory peptides are important mediators of the cross-communication between the nervous- and immune systems...

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...

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...

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 treatm...

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 Ig...

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 (P...

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...

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...

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 cell...

While desired for the cure of allergy, regulatory immune cell subsets and non-classical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunologica...

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-indu...

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 dogs, is associated with alterations in numbers and functions of immune cells at the sites of tumor progression. These tumor infiltrating immune cel...

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both anti-tumour immune surveillance and therapy. The i...

Natural killer (NK) cells are part of the innate immune system and combat pathogens and tumors by secreting pro-inflammatory cytokines like interferon gamma (IFN-γ) and by their cytotoxic action. Galanin is a neuropeptide also expressed in peripheral tissue where it impacts several physiological functions, including inflammation. The effects of gal...

Figure S1. 3D structure and topology of a prototypical lipocalin.

Galanin and its receptors (GAL1, GAL2, GAL3) modulate a range of neuronal, immune and vascular activities. In vivo administration of SNAP 37889 (1-phenyl-3-[[3-(trifluoromethyl)phenyl]imino]-1H-indol-2-one), a potent small non-peptidergic antagonist of GAL3, was reported to reduce anxiety- and depression-related behavior, ethanol consumption, and a...

Owners and their domestic animals via skin shedding and secretions, mutually exchange microbiomes, potential pathogens and innate immune molecules. Among the latter especially lipocalins are multifaceted: they may have an immunomodulatory function and, furthermore, they represent one of the most important animal allergen families. The amino acid id...

AimsPolymorphonuclear neutrophils are key players in innate immunity. The innate immune system needs to be tightly controlled to ensure proper activation but also no over-activation. Galanin has been shown to regulate inflammatory reactions, and therefore we aimed to elucidate the expression of galanin and its three receptors (GAL1-GAL3) in polymor...

Group B Streptococcus (GBS) has evolved several strategies to avoid host defences. We have shown that interaction of macrophages with GBS causes macrophage calpain activation, cytoskeletal disruption and apoptosis, consequences of intracellular calcium increase induced by membrane permeability alterations provoked by GBS-β-haemolysin. Open question...

The interaction of Glucocorticoid-Induced TNF receptor-family Related (GITR) protein with its ligand (GITRL) modulates different functions including immune/inflammatory response. These effects are consequent to intracellular signals activated by both GITR and GITRL. Previous results suggest that lack of GITR expression, in GITR(-/-) mice, decreases...

Objective: CD4(+)CD25(low)GITR(+) T lymphocytes expressing FoxP3 and showing regulatory function have been recently described in healthy donors (HD). The objective of the study was to investigate their presence and role in patients with primary SS (pSS). Methods: CD4(+)CD25(low)GITR(+) cells circulating in peripheral blood (PB) of patients with...

Neuropeptides participate in innate immunity and tolerance. Galanin is a neuropeptide with a widespread distribution in the central and peripheral nervous systems. Several in vivo studies indicate that galanin plays a role in inflammation. The aim of the present study was to identify immune cells expressing components of the galanin system includin...

Treg subsets play a role in sustaining peripheral tolerance, are characterized by markers such as forkhead winged-helix transcription factor (FOXP3) and CD25, and produce suppressive cytokines, such as IL-10 and TGF-β. Glucocorticoid-induced TNF receptor family-related (GITR) protein has been suggested to regulate Treg activity in mice. The aim of...

Glucocorticoid-Induced TNFR family Related gene (GITR), a Tumor Necrosis Factor Receptor Superfamily (TNFRSF) member involved in immune/inflammatory processes, has been previously shown to regulate T cell activation. To study GITR role in antigen presenting cells, we evaluated the capability of bone marrow derived dendritic cells (BMDC) from GITR(-...

Regulatory T cells (T(REG)) represent a T cell subset able to modulate immune response by suppressing autoreactive T-lymphocytes. The evidence of a reduced number and an impaired function of this cell population in autoimmune/inflammatory chronic diseases led to the hypothesis of its involvement in the pathogenesis of these disorders. Glucocorticoi...

The concept that regulatory T cells (Treg) play a key role in both development and maintenance of autoimmune response in rheumatic diseases is well accepted. In recent years, several studies analyzed Treg cell phenotype and function in systemic lupus erythematosus (SLE), the prototypical systemic autoimmune disorder in humans. Although qualitative...

Glucocorticoid-induced tumor necrosis factor receptor-related (GITR) protein is a costimulatory molecule that plays a role in inflammation so that GITR-Fc fusion protein can exert an anti-inflammatory effect. To investigate the mechanism by which GITR-Fc exerts its effects, we first used GITR knock-out (GITR(-/-)) mice to verify whether GITR ligand...

We evaluated the effect of GITR-Fc fusion protein (Glucocorticoid-Induced Tumor necrosis factor receptor-Related) against spinal cord injury (SCI) in GITR(-/-) and wild type (GITR(+/+)) mice. Notably, a less pronounced disease was induced in GITR(-/-) as compared to GITR(+/+) mice. Administration of GITR-Fc ameliorated SCI-induced inflammation in G...

CD28 is well characterized as a costimulatory molecule in T cell activation. Recent evidences indicate that TNFR superfamily members, including glucocorticoid-induced TNFR-related protein (GITR), act as costimulatory molecules. In this study, the relationship between GITR and CD28 has been investigated in murine CD8(+) T cells. When suboptimal dose...

Resistin could be the linkage between the adipose tissue and the insulin resistance. In humans, the role of resistin on metabolic and vascular homeostasis is not well defined. The aim of this study was to investigate the possible association between resistin expression and insulin resistance. We evaluated the relationship between monocyte expressio...

Glucocorticoid-induced TNFR-related (GITR) protein, a member of the tumor necrosis factor receptor superfamily, is expressed in many components of the innate and adaptive immune system and modulates their activation following interaction with its ligand (GITRL). Here we review and discuss results described in previous publications where the role of...

Glucocorticoid-induced TNFR-Related (GITR) protein is a member of the tumor necrosis factor receptor superfamily that modulates acquired and natural immune response. It is expressed in several cells and tissues, including T cells, natural killer cells, and, at lower levels, in cells of innate immunity. GITR is activated by its ligand, GITRL, mainly...

Glucocorticoids play a role in regulation of T lymphocytes homeostasis and development. In particular, glucocorticoid treatment induces massive apoptosis of CD4(+)CD8(+) double-positive (DP) thymocytes. This effect is due to many mechanisms, mainly driven by modulation of gene transcription. To find out which genes are modulated, we analyzed DP thy...

GITR (glucocorticoid-induced TNFR family related gene) is a member of the TNFR superfamily (TNFRSF) that is expressed in different cell types, including T lymphocytes. Because of a high homology in its cytoplasmic region with other known costimulatory members of the TNFRSF, we investigated whether GITR played a costimulatory role in T lymphocyte su...

Cell death and differentiation is a monthly research journal focused on the exciting field of programmed cell death and apoptosis. It provides a single accessible source of information for both scientists and clinicians, keeping them up-to-date with advances in the field. It encompasses programmed cell death, cell death induced by toxic agents, dif...