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Unlike conventional CD4+ T cells, which are phenotypically and functionally plastic, invariant NKT (iNKT) cells generally exist in a terminally differentiated state. Naïve CD4+ T cells can acquire alternative epigenetic states in response to different cues, but it remains unclear whether peripheral iNKT cells are epigenetically stable or malleable. Repetitive encounters of liver-resident iNKT cells (LiNKTs) with alpha-galactosylceramide (aGalCer)/CD1d-coated nanoparticles (NPs) can trigger their differentiation into a LiNKT cell subset expressing a T regulatory type 1 (TR1)-like (LiNKTR1) transcriptional signature. Here we dissect the epigenetic underpinnings of the LiNKT-LiNKTR1 conversion as compared to those underlying the peptide-major histocompatibility complex (pMHC)-NP-induced T-follicular helper (TFH)-to-TR1 transdifferentiation process. We show that gene upregulation during the LINKT-to-LiNKTR1 cell conversion is associated with demethylation of gene bodies, inter-genic regions, promoters and distal gene regulatory elements, in the absence of major changes in chromatin exposure or deposition of expression-promoting histone marks. In contrast, the naïve CD4+ T cell-to-TFH differentiation process involves extensive remodeling of the chromatin and the acquisition of a broad repertoire of epigenetic modifications that are then largely inherited by TFH cell-derived TR1 cell progeny. These observations indicate that LiNKT cells are epigenetically malleable and particularly susceptible to gene de-methylation. [ABSTRACT FROM AUTHOR]

Background: Ambient air pollution has been associated with COVID-19 disease severity and antibody response induced by infection. Objectives: We examined the association between long-term exposure to air pollution and vaccine-induced antibody response. METHODS: This study was nested in an ongoing population-based cohort, COVICAT, the GCAT-Genomes for Life cohort, in Catalonia, Spain, with multiple follow-ups. We drew blood samples in 2021 from 1,090 participants of 2,404 who provided samples in 2020, and we included 927 participants in this analysis. We measured immunoglobulin M (IgM), IgG, and IgA antibodies against five viral-target antigens, including receptor-binding domain (RBD), spike-protein (S), and segment spike-protein (S2) triggered by vaccines available in Spain. We estimated prepandemic (2018-2019) exposure to fine particulate matter [PM [less than or equal to] 2.5 [micro]m in aerodynamic diameter (P[M.sub.2.5])], nitrogen dioxide (N[O.sub.2]), black carbon (BC), and ozone ([O.sub.3]) using Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) models. We adjusted estimates for individual- and area-level covariates, time since vaccination, and vaccine doses and type and stratified by infection status. We used generalized additive models to explore the relationship between air pollution and antibodies according to days since vaccination. Results: Among vaccinated persons not infected by SARS-CoV-2 (n = 632), higher prepandemic air pollution levels were associated with a lower vaccine antibody response for IgM (1 month post vaccination) and IgG. Percentage change in geometric mean IgG levels per interquartile range of P[M.sub.2.5] (1.7 [micro]g/[m.sup.3]) were -8.1 (95% CI: - 15.9, 0.4) for RBD, -9.9 (-16.2, -3.1) for S, and -8.4 (-13.5, -3.0) for S2. We observed a similar pattern for N[O.sub.2] and BC and an inverse pattern for [O.sub.3]. Differences in IgG levels by air pollution levels persisted with time since vaccination. We did not observe an association of air pollution with vaccine antibody response among participants with prior infection (n = 295). Discussion: Exposure to air pollution was associated with lower COVID-19 vaccine antibody response. The implications of this association on the risk of breakthrough infections require further investigation. https://doi.org/10.1289/EHP11989, Introduction Air pollution has been associated with COVID-19 disease initially in ecological studies and later in cohort studies using individual data. (1-6) There are some differences between findings of individual-based [...]

BackgroundPrimary care is a major access point for the initial treatment of depression, but the management of these patients is far from optimal. The lack of time in primary care is one of the major difficulties for the delivery of evidence-based psychotherapy. During the last decade, research has focused on the development of brief psychotherapy and cost-effective internet-based interventions mostly based on cognitive behavioral therapy (CBT). Very little research has focused on alternative methods of treatment for depression using CBT. Thus, there is a need for research into other therapeutic approaches. ObjectiveThis study aimed to assess the effectiveness of 3 low-intensity, internet-based psychological interventions (healthy lifestyle psychoeducational program [HLP], focused program on positive affect promotion [PAPP], and brief intervention based on mindfulness [MP]) compared with a control condition (improved treatment as usual [iTAU]). MethodsA multicenter, 4-arm, parallel randomized controlled trial was conducted between March 2015 and March 2016, with a follow-up of 12 months. In total, 221 adults with mild or moderate major depression were recruited in primary care settings from 3 Spanish regions. Patients were randomly distributed to iTAU (n=57), HLP (n=54), PAPP (n=56), and MP (n=54). All patients received iTAU from their general practitioners. The main outcome was the Spanish version of the Patient Health Questionnaire-9 (PHQ-9) from pretreatment (time 1) to posttreatment (time 2) and up to 6 (time 3) and 12 (time 4) months’ follow-up. Secondary outcomes included the visual analog scale of the EuroQol, the Short-Form Health Survey (SF-12), the Positive and Negative Affect Schedule (PANAS), and the Pemberton Happiness Index (PHI). We conducted regression models to estimate outcome differences along study stages. ResultsA moderate decrease was detected in PHQ-9 scores from HLP (β=–3.05; P=.01) and MP (β=–3.00; P=.01) compared with iTAU at posttreatment. There were significant differences between all intervention groups and iTAU in physical SF-12 scores at 6 months after treatment. Regarding well-being, MP and PAPP reported better PHI results than iTAU at 6 months post treatment. PAPP intervention significantly decreased PANAS negative affect scores compared with iTAU 12 months after treatment. ConclusionsThe low-intensity, internet-based psychological interventions (HLP and MP) for the treatment of depression in primary care are more effective than iTAU at posttreatment. Moreover, all low-intensity psychological interventions are also effective in improving medium- and long-term quality of life. PAPP is effective for improving health-related quality of life, negative affect, and well-being in patients with depression. Nevertheless, it is important to examine possible reasons that could be implicated for PAPP not being effective in reducing depressive symptomatology; in addition, more research is still needed to assess the cost-effectiveness analysis of these interventions. Trial RegistrationISRCTN Registry ISRCTN82388279; http://www.isrctn.com/ISRCTN82388279 International Registered Report Identifier (IRRID)RR2-10.1186/s12888-015-0475-0

Despite the dynamic nature of communities, most research typically treated interaction networks as static entities, and only a few analysed the spatial and the temporal scales simultaneously. Here, we used spatial and temporal multilayer networks to explore the persistence of species and interactions in space and time, as well as the variation of species role (centrality) according to biotic factors. We further investigated, for the first time, the spatio‐temporal variation in multilayer network structure. Species exhibited substantial turnover across time mainly due to differences in species phenology. In contrast, interaction turnover was more pronounced across habitats, which seems to be a common strategy of pollinators to adjust interactions spatially to different ecological scenarios. Plant species were comparatively more important to the cohesiveness of spatial than temporal networks, whereas the centrality of pollinators correlated between scales. The importance of plant species fluctuated temporally due mainly to changes in flower density, whereas that of pollinators fluctuated in space and time according to their relative abundance. Module composition was highly unstable in time. Species were highly capable of changing partners and module affiliation across both scales. We conclude that plant–pollinator interactions are highly dynamic in space and time, and that there are differences between plants and pollinators in their use of resources across habitats and subseasons with implications for the understanding of functional connectivity and multilayer structure. [ABSTRACT FROM AUTHOR]

Regulatory T cells hold promise as targets for therapeutic intervention in autoimmunity, but approaches capable of expanding antigen-specific regulatory T cells in vivo are currently not available. Here we show that systemic delivery of nanoparticles coated with autoimmune-disease-relevant peptides bound to major histocompatibility complex class II (pMHCII) molecules triggers the generation and expansion of antigen-specific regulatory [CD4.sup.+] T cell type 1 ([T.sub.R]1)-like cells in different mouse models, including mice humanized with lymphocytes from patients, leading to resolution of established autoimmune phenomena. Ten pMHCII-based nanomedicines show similar biological effects, regardless of genetic background, prevalence of the cognate T-cell population or MHC restriction. These nanomedicines promote the differentiation of disease-primed autoreactive T cells into [T.sub.R]1-like cells, which in turn suppress autoantigen- loaded antigen-presenting cells and drive the differentiation of cognate B cells into disease-suppressing regulatory B cells, without compromising systemic immunity. pMHCII-based nanomedicines thus represent a new class of drugs, potentially useful for treating a broad spectrum of autoimmune conditions in a disease-specific manner., Autoimmune diseases such as type 1 diabetes (T1D), multiple sclerosis and rheumatoid arthritis result from chronic autoimmune responses involving T cells and B cells recognizing numerous antigenic epitopes on incompletely [...]