The Role of T cell PPAR γ in mice with experimental inflammatory bowel disease

<p>Abstract</p> <p>Background</p> <p>Peroxisome proliferator-activated receptor γ (PPAR γ) is a nuclear receptor whose activation has been shown to modulate macrophage and T cell-mediated inflammation. The objective of this study was to investigate the mechanisms by which the deletion of PPAR γ in T cells modulates immune cell distribution and colonic gene expression and the severity of experimental IBD.</p> <p>Methods</p> <p>PPAR γ flfl; CD4 Cre⁺(CD4cre) or Cre- (WT) mice were challenged with 2.5% dextran sodium sulfate in their drinking water for 0, 2, or 7 days. Mice were scored on disease severity both clinically and histopathologically. Flow cytometry was used to assess lymphocyte and macrophage populations in the blood, spleen, and mesenteric lymph nodes (MLN). Global gene expression in colonic mucosa was profiled using Affymetrix microarrays.</p> <p>Results</p> <p>The deficiency of PPAR γ in T cells accelerated the onset of disease and body weight loss. Examination of colon histopathology revealed significantly greater epithelial erosion, leukocyte infiltration, and mucosal thickening in the CD4cre mice on day 7. CD4cre mice had more CD8⁺T cells than WT mice and fewer CD4⁺FoxP3⁺regulatory T cells (Treg) and IL10⁺CD4⁺T cells in blood and MLN, respectively. Transcriptomic profiling revealed around 3000 genes being transcriptionally altered as a result of DSS challenge in CD4cre mice. These included up-regulated mRNA expression of adhesion molecules, proinflammatory cytokines interleukin-6 (IL-6) and IL-1β, and suppressor of cytokine signaling 3 (SOCS-3) on day 7. Gene set enrichment analysis (GSEA) showed that the ribosome and Krebs cycle pathways were downregulated while the apoptosis pathway was upregulated in colons of mice lacking PPAR γ in T cells.</p> <p>Conclusions</p> <p>The expression of PPAR γ in T cells is involved in preventing gut inflammation by regulating colonic expression of adhesion molecules and inflammatory mediators at later stages of disease while favoring the recruitment of Treg to the mucosal inductive sites.</p

The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis

T cell development results in the generation of both mature αβ and γδ T cells. While αβ T cells predominate in secondary lymphoid organs, γδ T cells are more abundant in mucosal tissues. PU.1, an Ets family transcription factor, also identified as the spleen focus forming virus proviral integration site-1 (Sfpi1) is essential for early stages of T cell development, but is down regulated during the DN T-cell stage.In this study, we show that in mice specifically lacking PU.1 in T cells using an lck-Cre transgene with a conditional Sfpi1 allele (Sfpi1(lck-/-)) there are increased numbers of γδ T cells in spleen, thymus and in the intestine when compared to wild-type mice. The increase in γδ T cell numbers in PU.1-deficient mice is consistent in γδ T cell subsets identified by TCR variable regions. PU.1-deficient γδ T cells demonstrate greater proliferation in vivo and in vitro.The increase of γδ T cell numbers in Lck-Cre deleter strains, where deletion occurs after PU.1 expression is diminished, as well as the observation that PU.1-deficient γδ T cells have greater proliferative responses than wild type cells, suggests that PU.1 effects are not developmental but rather at the level of homeostasis. Thus, our data shows that PU.1 has a negative influence on γδ T cell expansion

Study protocol of a randomized controlled trial to assess safety of teleconsultation compared with face-to-face consultation: the ECASeT study

BackgroundThe use of remote consultation modalities has exponentially grown in the past few years, particularly since the onset of the COVID-19 pandemic. Although a huge body of the literature has described the use of phone (tele) and video consultations, very few of the studies correspond to randomized controlled trials, and none of them has assessed the safety of these consultation modalities as the primary objective. The primary objective of this trial was to assess the safety of remote consultations (both video and teleconsultation) in the follow-up of patients in the hospital setting.MethodsMulticenter, randomized controlled trial being conducted in four centers of an administrative healthcare area in Catalonia (North-East Spain). Participants will be screened from all individuals, irrespective of age and sex, who require follow-up in outpatient consultations of any of the departments involved in the study. Eligibility criteria have been established based on the local guidelines for screening patients for remote consultation. Participants will be randomly allocated into one of the two study arms: conventional face-to-face consultation (control) and remote consultation, either teleconsultation or video consultation (intervention). Routine follow-up visits will be scheduled at a frequency determined by the physician based on the diagnostic and therapy of the baseline disease (the one triggering enrollment). The primary outcome will be the number of adverse reactions and complications related to the baseline disease. Secondary outcomes will include non-scheduled visits and hospitalizations, as well as usability features of remote consultations. All data will either be recorded in an electronic clinical report form or retrieved from local electronic health records. Based on the complications and adverse reaction rates reported in the literature, we established a target sample size of 1068 participants per arm. Recruitment started in May 2022 and is expected to end in May 2024.DiscussionThe scarcity of precedents on the assessment of remote consultation modalities using randomized controlled designs challenges making design decisions, including recruitment, selection criteria, and outcome definition, which are discussed in the manuscript.Trial registrationNCT05094180. The items of the WHO checklist for trial registration are available in Additional file 1. Registered on 24 November 2021

Study protocol of a randomized controlled trial to assess safety of teleconsultation compared with face-to-face consultation: the ECASeT study

Abstract Background The use of remote consultation modalities has exponentially grown in the past few years, particularly since the onset of the COVID-19 pandemic. Although a huge body of the literature has described the use of phone (tele) and video consultations, very few of the studies correspond to randomized controlled trials, and none of them has assessed the safety of these consultation modalities as the primary objective. The primary objective of this trial was to assess the safety of remote consultations (both video and teleconsultation) in the follow-up of patients in the hospital setting. Methods Multicenter, randomized controlled trial being conducted in four centers of an administrative healthcare area in Catalonia (North-East Spain). Participants will be screened from all individuals, irrespective of age and sex, who require follow-up in outpatient consultations of any of the departments involved in the study. Eligibility criteria have been established based on the local guidelines for screening patients for remote consultation. Participants will be randomly allocated into one of the two study arms: conventional face-to-face consultation (control) and remote consultation, either teleconsultation or video consultation (intervention). Routine follow-up visits will be scheduled at a frequency determined by the physician based on the diagnostic and therapy of the baseline disease (the one triggering enrollment). The primary outcome will be the number of adverse reactions and complications related to the baseline disease. Secondary outcomes will include non-scheduled visits and hospitalizations, as well as usability features of remote consultations. All data will either be recorded in an electronic clinical report form or retrieved from local electronic health records. Based on the complications and adverse reaction rates reported in the literature, we established a target sample size of 1068 participants per arm. Recruitment started in May 2022 and is expected to end in May 2024. Discussion The scarcity of precedents on the assessment of remote consultation modalities using randomized controlled designs challenges making design decisions, including recruitment, selection criteria, and outcome definition, which are discussed in the manuscript. Trial registration NCT05094180. The items of the WHO checklist for trial registration are available in Additional file 1. Registered on 24 November 2021

Hispano-Americans in Europe: what do we know about their health status and determinants? A scoping review.

BACKGROUND: Policy makers and health practitioners are in need of guidance to respond to the growing geographic mobility of Hispano-American migrants in Europe. Drawing from contributions from epidemiology, social sciences, demography, psychology, psychiatry and economy, this scoping review provides an up-to-date and comprehensive synthesis of studies addressing the health status and determinants of this population. We describe major research gaps and suggest specific avenues of further inquiry. METHODS: We identified systematically papers that addressed the concepts "health" and "Hispano Americans" indexed in five data bases from Jan 1990 to May 2014 with no language restrictions. We screened the 4,464 citations retrieved against exclusion criteria and classified 193 selected references in 12 thematic folders with the aid of the reference management software ENDNOTE X6. After reviewing the full text of all papers we extracted relevant data systematically into a table template to facilitate the synthesising process. RESULTS: Most studies focused on a particular disease, leaving unexplored the interlinkages between different health conditions and how these relate to legislative, health services, environmental, occupational, and other health determinants. We elucidated some consistent results but there were many heterogeneous findings and several popular beliefs were not fully supported by empirical evidence. Few studies adopted a trans-national perspective and many consisted of cross-sectional descriptions that considered "Hispano-Americans" as a homogeneous category, limiting our analysis. Our results are also constrained by the availability and varying quality of studies reviewed./nCONCLUSIONS:/nBurgeoning research has produced some consistent findings but there are huge gaps in knowledge. To prevent unhelpful generalisations we need a more holistic and nuanced understanding of how mobility, ethnicity, income, gender, legislative status, employment status, working conditions, neighbourhood characteristics and social status intersect with demographic variables and policy contexts to influence the health of the diverse Hispano-American populations present in Europe