Activation-induced cytidine deaminase (AID) linking immunity, chronic inflammation, and cancer

Activation-induced cytidine deaminase (AID) is critically involved in class switch recombination and somatic hypermutation of Ig loci resulting in diversification of antibodies repertoire and production of high-affinity antibodies and as such represents a physiological tool to introduce DNA alterations. These processes take place within germinal centers of secondary lymphoid organs. Under physiological conditions, AID is expressed predominantly in activated B lymphocytes. Because of the mutagenic and recombinogenic potential of AID, its expression and activity is tightly regulated on different levels to minimize the risk of unwanted DNA damage. However, chronic inflammation and, probably, combination of other not-yet-identified factors are able to create a microenvironment sufficient for triggering an aberrant AID expression in B cells and, importantly, in non-B-cell background. Under these circumstances, AID may target also non-Ig genes, including cancer-related genes as oncogenes, tumor suppressor genes, and genomic stability genes, and modulate both genetic and epigenetic information. Despite ongoing progress, the complete understanding of fundamental aspects is still lacking as (1) what are the crucial factors triggering an aberrant AID expression/activity including the impact of Th2-driven inflammation and (2) to what extent may aberrant AID in human non-B cells lead to abnormal cell state associated with an increased rate of genomic alterations as point mutations, small insertions or deletions, and/or recurrent chromosomal translocations during solid tumor development and progression

Occupational physical activity: the good, the bad, and the proinflammatory

BackgroundPhysical activity (PA) is beneficial for preventing several conditions associated with underlying chronic inflammation, e. g., cardiovascular disease (CVD) and cancer. While an active lifestyle appears to have anti-inflammatory effects, high levels of occupational PA (OPA) were associated with inflammation and elevated mortality risks. We aimed to summarize the current knowledge (1) on the association between inflammation and OPA and (2) its implications for health and mortality.Methods and resultsThis mini-review summarized relevant literature published before January 2023 using established scientific databases and sources. For the primary outcome, observational studies (S) reporting immunological effects (O) in subjects (P), with high (I) vs. low OPA (C), were included. For secondary outcomes, i.e., morbidity and mortality associated with inflammatory processes, (systematic) reviews were included. While “active” occupations and “moderate” OPA appear to have beneficial effects, low (particularly sedentary) and “high-intensity” OPA (particularly including heavy lifting tasks) were associated with inflammation and (CVD and cancer-related) mortality; higher leisure-time PA has been almost consistently associated with lower proinflammatory markers and all-cause mortality risks. Workplace interventions appear to counter some of the observed health effects of unfavorable work strain.ConclusionThe few studies addressing OPA “intensity” and inflammatory markers are largely heterogeneous regarding OPA classification and confounder control. Sedentary and “heavy” OPA appear to promote proinflammatory effects. In addition to targeted management of work-related physical strain and hazardous environmental co-factors, occupational health providers should focus on employer-initiated exercise interventions and the promotion of leisure-time PA

The human side of animal experimentation: A qualitative, exploratory study into workrelated stress and coping in animal experimenters

Besides the pervasive controversy of animal experimentation in society, ethics and science, the human experimenter side of laboratory animal studies is a relatively underrepresented topic in human-animal interaction research. Few studies have addressed scientists’ stress responses to animal experiments. The main aim of this study was to assess work-related stress by means of salivary cortisol secretion, coping strategies, self-esteem, pet attitude and personality traits in academic researchers who regularly perform invasive animal experiments. Invitation to participate in the study resulted in a response rate of 15.4% of 65 invited scientists, of which only four (6.15%) completed data collection. Study participants carried out saliva sampling on working days with and without animal experiments, completed a semi-structured qualitative interview and psychological questionnaires. Salivary cortisol (SC) was measured via enzyme immunoassay. The results indicate that animal experimenters used problem-focused and emotion-focused coping strategies. Three participants reached above average values in self-esteem. Pet attitudes scores were moderately positive. Three out of four animal experimenters reached high scores on the personality dimensions "openness to experience", "agreeableness" and "conscientiousness". In the absence of an acute increase in SC related to animal experimentation, two out of four participants exhibited an altered circadian pattern of SC secretion only on working days with animal experiments. Although and as a matter of fact because only four of 65 invited scientists volunteered to participate, we discussed the seemingly low willingness of researchers to participate in such a study based on a theoretical analysis, particularly highlighting the concept of deindividuation and provide suggestions for future research

Modulatory impact of cinnamaldehyde on immune cells is partly due to induction of apoptosis.

Cinnamaldehyde (CA) has been reported to have antiinflammatory, anti-bacterial, anti-fungal, chemoprotective and anti-carcinogenic activity. Here, we further investigated the immune-modulating capacity of CA

Formulations for Allergen Immunotherapy in Human and Veterinary Patients: New Candidates on the Horizon

Allergen immunotherapy is currently the only causal treatment for allergic diseases in human beings and animals. It aims to re-direct the immune system into a tolerogenic or desensitized state. Requirements include clinical efficacy, safety, and schedules optimizing patient or owner compliance. To achieve these goals, specific allergens can be formulated with adjuvants that prolong tissue deposition and support uptake by antigen presenting cells, and/or provide a beneficial immunomodulatory action. Here, we depict adjuvant formulations being investigated for human and veterinary allergen immunotherapy

Activation-Induced Cytidine Deaminase (AID)-Associated Multigene Signature to Assess Impact of AID in Etiology of Diseases with Inflammatory Component

Activation-induced cytidine deaminase (AID) is expressed in B cells within germinal centers and is critically involved in class switch recombination and somatic hypermutation of immunoglobulin loci. Functionally active AID can additionally be detected within ectopic follicular structures developed at sites of chronic inflammation. Furthermore, AID may target non-Ig genes in B- and non-B-cell background. Therefore, AID-associated effects are of increasing interest in disease areas such as allergy, inflammation, autoimmunity, and cancer

The High Affinity IgE Receptor FcεRI Is Expressed by Human Intestinal Epithelial Cells

IgE antibodies play a paramount role in the pathogenesis of various intestinal disorders. To gain insights in IgE-mediated pathophysiology of the gut, we investigated the expression of the high affinity IgE receptor Fc epsilonRI in human intestinal epithelium.Fc epsilonRI alpha-chain, as detected by immunohistochemistry, was positive in epithelial cells for eight of eleven (8/11) specimens from colon cancer patients and 5/11 patients with inflammation of the enteric mucosa. The Fc epsilonRIalpha positive epithelial cells co-expressed Fc epsilonRIgamma, whereas with one exception, none of the samples was positive for the beta-chain in the epithelial layer. The functionality of Fc epsilonRI was confirmed in situ by human IgE binding. In experiments with human intestinal tumor cell lines, subconfluent Caco-2/TC7 and HCT-8 cells were found to express the alpha- and gamma-chains of Fc epsilonRI and to bind IgE, whereas confluent cells were negative for gamma-chains.Our data provide the first evidence that the components of a functional Fc epsilonRI are in vitro expressed by the human intestinal epithelial cells depending on differentiation and, more importantly, in situ in epithelia of patients with colon cancer or gastrointestinal inflammations. Thus, a contribution of Fc epsilonRI either to immunosurveillance or pathophysiology of the intestinal epithelium is suggested