Empowering youth sport and acculturation: examining the hosts’ perspective in Greek adolescents

Objectives: Research on the role of sport as a context for the acculturation of young migrants has mainly focused on migrant populations. Considering that acculturation is a two-way process involving both the migrant and the host populations, research investigating the perspective of the hosts will enhance our understanding of the acculturation process. The purpose of the present study was to explore acculturation attitudes and perceptions of adolescents from the host population as a function of sport participation. Furthermore, for those adolescents participating in sport, the role of the sport motivational climate and its relation to acculturation attitudes was investigated. Design and Method: A cross-sectional quantitative design was adopted. Participants were 626 (316 girls) Greek, high school students (13.88 ± 1.01 years of age). Among them, 271 (92 girls) were athletes competing in individual and team sports. While all participants completed measures of acculturation attitudes, the athletes additionally completed measures of motivational climate, basic need satisfaction, and controlling coaching behavior. Results: Athletes scored higher than non-athletes on attitudes towards multicultural contact. Analysis of structural models revealed that a motivational climate characterized by a mastery climate, supportive of the needs of autonomy, competence, and relatedness, was positively linked to attitudes favoring migrants’ maintenance of their culture and development of interaction with the host culture, whereas a motivational climate characterized by a performance climate and controlling coaching behavior was negatively linked to such attitudes. Conclusion: These findings provide useful insights concerning the perspectives of the host population regarding migrants’ acculturation and the role motivational climate play in promoting integration

The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease

Foxa2, a member of the Forkhead box (Fox) family of transcription factors, plays an important role in the regulation of lung function and lung tissue homeostasis. FOXA2 expression is reduced in the lung and airways epithelium of asthmatic patients and in mice absence of Foxa2 from the lung epithelium contributes to airway inflammation and goblet cell hyperplasia. Here we demonstrate a novel role for Foxa2 in the regulation of T helper differentiation and investigate its impact on lung inflammation. Conditional deletion of Foxa2 from T-cells led to increased Th2 cytokine secretion and differentiation, but decreased Th1 differentiation and IFN-γ expression in vitro. Induction of mouse allergic airway inflammation resulted in more severe disease in the conditional Foxa2 knockout than in control mice, with increased cellular infiltration to the lung, characterized by the recruitment of eosinophils and basophils, increased mucus production and increased production of Th2 cytokines and serum IgE. Thus, these experiments suggest that Foxa2 expression in T-cells is required to protect against the Th2 inflammatory response in allergic airway inflammation and that Foxa2 is important in T-cells to maintain the balance of effector cell differentiation and function in the lung

Systemic Pharmacological Smoothened Inhibition Reduces Lung T-Cell Infiltration and Ameliorates Th2 Inflammation in a Mouse Model of Allergic Airway Disease

Allergic asthma is a common inflammatory airway disease in which Th2 immune response and inflammation are thought to be triggered by inhalation of environmental allergens. Many studies using mouse models and human tissues and genome-wide association have indicated that Sonic Hedgehog (Shh) and the Hedgehog (Hh) signaling pathway are involved in allergic asthma and that Shh is upregulated in the lung on disease induction. We used a papain-induced mouse model of allergic airway inflammation to investigate the impact of systemic pharmacological inhibition of the Hh signal transduction molecule smoothened on allergic airway disease induction and severity. Smoothened-inhibitor treatment reduced the induction of Shh, IL-4, and IL-13 in the lung and decreased serum IgE, as well as the expression of Smo, Il4, Il13, and the mucin gene Muc5ac in lung tissue. Smoothened inhibitor treatment reduced cellular infiltration of eosinophils, mast cells, basophils, and CD4+ T-cells to the lung, and eosinophils and CD4+ T-cells in the bronchoalveolar lavage. In the mediastinal lymph nodes, smoothened inhibitor treatment reduced the number of CD4+ T-cells, and the cell surface expression of Th2 markers ST2 and IL-4rα and expression of Th2 cytokines. Thus, overall pharmacological smoothened inhibition attenuated T-cell infiltration to the lung and Th2 function and reduced disease severity and inflammation in the airway

IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation

T cells differentiated more efficiently to Th1, whereas Th2 differentiation was inhibited. Ifitm-family-deficient mice, but not Ifitm3-deficient mice, were less susceptible than WT to induction of allergic airways disease, with a weaker Th2 response and less severe disease and lower Il4 but higher Ifng expression and IL-27 secretion. Thus, the Ifitm family is important in adaptive immunity, influencing Th1/Th2 polarization, and Th2 immunopathology

Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation.

Hedgehog (Hh) proteins regulate development and tissue homeostasis, but their role in atopic dermatitis (AD) remains unknown. We found that on induction of mouse AD, Sonic Hedgehog (Shh) expression in skin, and Hh pathway action in skin T cells were increased. Shh signaling reduced AD pathology and the levels of Shh expression determined disease severity. Hh-mediated transcription in skin T cells in AD-induced mice increased Treg populations and their suppressive function through increased active transforming growth factor-β (TGF-β) in Tregs signaling to skin T effector populations to reduce disease progression and pathology. RNA sequencing of skin CD4+ T cells from AD-induced mice demonstrated that Hh signaling increased expression of immunoregulatory genes and reduced expression of inflammatory and chemokine genes. Addition of recombinant Shh to cultures of naive human CD4+ T cells in iTreg culture conditions increased FOXP3 expression. Our findings establish an important role for Shh upregulation in preventing AD, by increased Gli-driven Treg cell-mediated immune suppression, paving the way for a potential new therapeutic strategy.MRCWellcome TrustGreat Ormond Street Hospital Children’s Charity (GOSHCC)PfizerNational Institute for Health Research Biomedical Research Centre at GOS

Update on current views and advances on RSV infection (Review).

Respiratory syncytial virus (RSV) infection represents an excellent paradigm of precision medicine in modern paediatrics and several clinical trials are currently performed in the prevention and management of RSV infection. A new taxonomic terminology for RSV was recently adopted, while the diagnostic and omics techniques have revealed new modalities in the early identification of RSV infections and for better understanding of the disease pathogenesis. Coordinated clinical and research efforts constitute an important step in limiting RSV global predominance, improving epidemiological surveillance, and advancing neonatal and paediatric care. This review article presents the key messages of the plenary lectures, oral presentations and posters of the '5th workshop on paediatric virology' (Sparta, Greece, 12th October 2019) organized by the Paediatric Virology Study Group, focusing on recent advances in the epidemiology, pathogenesis, diagnosis, prognosis, clinical management and prevention of RSV infection in childhood

Foxa1 and Foxa2 in thymic epithelial cells (TEC) regulate medullary TEC and regulatory T-cell maturation

The Foxa1 and Foxa2 transcription factors are essential for mouse development. Here we show that they are expressed in thymic epithelial cells (TEC) where they regulate TEC development and function, with important consequences for T-cell development. TEC are essential for T-cell differentiation, lineage decisions and repertoire selection. Conditional deletion of Foxa1 and Foxa2 from murine TEC led to a smaller thymus with a greater proportion of TEC and a greater ratio of medullary to cortical TEC. Cell-surface MHCI expression was increased on cortical TEC in the conditional Foxa1Foxa2 knockout thymus, and MHCII expression was reduced on both cortical and medullary TEC populations. These changes in TEC differentiation and MHC expression led to a significant reduction in thymocyte numbers, reduced positive selection of CD4+CD8+ cells to the CD4 lineage, and increased CD8 cell differentiation. Conditional deletion of Foxa1 and Foxa2 from TEC also caused an increase in the medullary TEC population, and increased expression of Aire, but lower cell surface MHCII expression on Aire-expressing mTEC, and increased production of regulatory T-cells. Thus, Foxa1 and Foxa2 in TEC promote positive selection of CD4SP T-cells and modulate regulatory T-cell production and activity, of importance to autoimmunity

The role of Hedgehog signalling in atopic dermatitis

Hedgehog (Hh) proteins are morphogens which regulate embryonic development and adult tissue homeostasis, with distinct outcomes dependent on the strength and duration of their signals. In skin, aberrant Hh pathway activation is linked to cancer and malformations, but the role of the pathway in skin inflammation remains largely unknown. Here I show that the Hh signalling pathway modulates the induction and pathology of mouse atopic dermatitis. Sonic hedgehog (Shh) and Hh pathway target genes were upregulated on induction of atopic dermatitis, and the Hh pathway was activated in skin T cells, showing that they respond in vivo to Hh signals secreted from the skin. Higher Shh upregulation reduced skin inflammation in mice, whereas pharmacological Smoothened-inhibition exacerbated skin pathology and reduced Shh upregulation. Hh-signalling to T cells prevented skin inflammation on induction of dermatitis, while inhibition of Hh-mediated transcription in T cells substantially exacerbated the disease. RNA-sequencing analysis of skin CD4+ T cells from mice with chronic atopic dermatitis revealed decreased expression of immune regulatory genes in mice with conditional inhibition of Hh-mediated transcription in T cells, and increased expression of inflammatory and chemokine genes. In contrast, constitutive Hh mediated transcription in T cells led to increased expression of immune regulatory genes in skin CD4+ T cells from mice with chronic atopic dermatitis and protected against inflammation. Hh-mediated transcription in T cells resulted in increased regulatory T (Treg) cells in the periphery and skin of dermatitis-induced mice, and increased TGF-β expression, supporting their immunoregulatory phenotype, whereas, inhibition of T cell specific Hh-mediated transcription, resulted in impaired Treg function, which permitted progression of skin inflammation. Thus, my data demonstrated a critical role for the Hh pathway through Shh upregulation, in the prevention of skin inflammation through upregulation of Shh signalling to T cells to increase Treg populations and promote their immunoregulatory function. This opens the possibility of novel therapeutic strategies for chronic inflammatory skin diseases and conversely suggests that Hh inhibitors could be used to enhance T cell immunity to Hh-secreting tumours

Sonic Hedgehog signalling in the regulation of barrier tissue homeostasis and inflammation

Epithelial barrier tissues such as the skin and airway form an essential interface between the mammalian host and its external environment. These physical barriers are crucial to prevent damage and disease from environmental insults and allergens. Failure to maintain barrier function against such risks can lead to severe inflammatory disorders, including atopic dermatitis and asthma. Here, we discuss the role of the morphogen Sonic Hedgehog in postnatal skin and lung and the impact of Shh signalling on repair, inflammation, and atopic disease in these tissues.Our research is funded by the MRC (MR/S037764/1 and MR/P00084/1) and BBSRC (BB/T020970/1)

Regulation of Adaptive Tumor Immunity by Non-Coding RNAs

© 2021 by the authors.Cancer immunology research has mainly focused on the role of protein-coding genes in regulating immune responses to tumors. However, despite more than 70% of the human genome is transcribed, less than 2% encodes proteins. Many non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have been identified as critical regulators of immune cell development and function, suggesting that they might play important roles in orchestrating immune responses against tumors. In this review, we summarize the scientific advances on the role of ncRNAs in regulating adaptive tumor immunity, and discuss their potential therapeutic value in the context of cancer immunotherapy.Our laboratory is funded by grants RTI2018-100008-A-I00 by MCIN/AEI/10.13039/ 501100011033/ and FEDER “Una manera de hacer Europa”, LAB-AECC 2020 from Spanish Association Against Cancer, SI1-PJI-2019-00241 from Community of Madrid, and merit award RyC-21155 funded by MCIN/AEI/10.13039/501100011033 and FSE “El FSE invierte en tu futuro” to A.G.-M., E.P. is supported by the FJC2019-040779-I fellowship funded by MCIN/AEI/10.13039/501100011033, L.G.-R. by the PRE2019-087940 fellowship funded by MCIN/AEI/10.13039/501100011033 and FSE “El FSE invierte en tu futuro”, and M.d.P.G.-M. by a FPI fellowship from Universidad Autónoma de Madrid.Peer reviewe