Hunger, temptation, and dietary adherence during weight management.

Preliminary evidence suggests that hunger and temptation may predict nonadherence to dietary intake goals; however, no studies have investigated the potential interaction between hunger and temptation in relation to dietary nonadherence nor have any investigated whether these associations may be different after the end of active behavioral intervention. Thus, the current study examined the week-to-week associations between hunger, temptation, and dietary adherence in 74 adults with overweight or obesity (mean ± SD age = 50.7 ± 10.4, BMI = 31.2 ± 4.5 kg/m2) enrolled in a 12-week, Internet-based weight loss program followed by a 40-week post-intervention observational maintenance period. Each week during the study, participants completed a questionnaire on which they rated their hunger, temptation, and dietary adherence on 7-point scales. Multilevel models demonstrated that higher levels of hunger and temptation were associated with lower ratings of dietary adherence during the same week, ps < 0.0001, such that 1-point higher ratings of hunger or temptation were associated with 0.2- and 0.5-point lower ratings of dietary adherence, respectively. Further, there was an interaction between hunger and temptation such that the association between temptation and dietary nonadherence was stronger when ratings of hunger were lower, p = .028. There were no differences in associations between the initial weight loss period and the maintenance period. Results suggest that hunger and temptation may serve as potential treatment targets for interventions aimed at improving adherence to dietary intake goals. Future studies should investigate whether interventions targeting hunger and temptation can improve dietary adherence and weight loss outcomes.

Widespread Tau-Specific CD4 T Cell Reactivity in the General Population.

Tau protein is found to be aggregated and hyperphosphorylated (p-tau) in many neurologic disorders, including Parkinson disease (PD) and related parkinsonisms, Alzheimer disease, traumatic brain injury, and even in normal aging. Although not known to produce autoimmune responses, we hypothesized that the appearance of aggregated tau and p-tau with disease could activate the immune system. We thus compared T cell responses to tau and p-tau-derived peptides between PD patients, age-matched healthy controls, and young healthy controls (<35 y old; who are less likely to have high levels of tau aggregates). All groups exhibited CD4+ T cell responses to tau-derived peptides, which were associated with secretion of IFN-γ, IL-5, and/or IL-4. The PD and control participants exhibited a similar magnitude and breadth of responses. Some tau-derived epitopes, consisting of both unmodified and p-tau residues, were more highly represented in PD participants. These results were verified in an independent set of PD and control donors (either age-matched or young controls). Thus, T cells recognizing tau epitopes escape central and peripheral tolerance in relatively high numbers, and the magnitude and nature of these responses are not modulated by age or PD disease.

Microbiota epitope similarity either dampens or enhances the immunogenicity of disease-associated antigenic epitopes.

The microbiome influences adaptive immunity and molecular mimicry influences T cell reactivity. Here, we evaluated whether the sequence similarity of various antigens to the microbiota dampens or increases immunogenicity of T cell epitopes. Sets of epitopes and control sequences derived from 38 antigenic categories (infectious pathogens, allergens, autoantigens) were retrieved from the Immune Epitope Database (IEDB). Their similarity to microbiome sequences was calculated using the BLOSUM62 matrix. We found that sequence similarity was associated with either dampened (tolerogenic; e.g. most allergens) or increased (inflammatory; e.g. Dengue and West Nile viruses) likelihood of a peptide being immunogenic as a function of epitope source category. Ten-fold cross-validation and validation using sets of manually curated epitopes and non-epitopes derived from allergens were used to confirm these initial observations. Furthermore, the genus from which the microbiome homologous sequences were derived influenced whether a tolerogenic versus inflammatory modulatory effect was observed, with Fusobacterium most associated with inflammatory influences and Bacteroides most associated with tolerogenic influences. We validated these effects using PBMCs stimulated with various sets of microbiome peptides. "Tolerogenic" microbiome peptides elicited IL-10 production, "inflammatory" peptides elicited mixed IL-10/IFNγ production, while microbiome epitopes homologous to self were completely unreactive for both cytokines. We also tested the sequence similarity of cockroach epitopes to specific microbiome sequences derived from households of cockroach allergic individuals and non-allergic controls. Microbiomes from cockroach allergic households were less likely to contain sequences homologous to previously defined cockroach allergens. These results are compatible with the hypothesis that microbiome sequences may contribute to the tolerization of T cells for allergen epitopes, and lack of these sequences might conversely be associated with increased likelihood of T cell reactivity against the cockroach epitopes. Taken together this study suggests that microbiome sequence similarity influences immune reactivity to homologous epitopes encoded by pathogens, allergens and auto-antigens.