Tuft cell IL-17RB restrains IL-25 bioavailability and reveals context-dependent ILC2 hypoproliferation.

The tuft cell-ILC2 circuit orchestrates rapid type 2 responses upon detecting microbe-derived succinate and luminal helminths. Our findings delineate key mechanistic steps, involving IP3R2 engagement and Ca 2+ flux, governing IL-25 production by tuft cells triggered by succinate detection. While IL-17RB plays a pivotal intrinsic role in ILC2 activation, it exerts a regulatory function in tuft cells. Tuft cells exhibit constitutive Il25 expression, placing them in an anticipatory state that facilitates rapid production of IL-25 protein for ILC2 activation. Tuft cell IL-17RB is crucial for restraining IL-25 bioavailability, preventing excessive tonic ILC2 stimulation due to basal Il25 expression. Suboptimal ILC2 stimulation by IL-25 resulting from tuft cell Il17rb -deficiency or prolonged succinate exposure induces a state of hypoproliferation in ILC2s, also observed in chronic helminth infection. Our study offers critical insights into the regulatory dynamics of IL-25 in this circuit, highlighting the delicate tuning required for responses to diverse luminal states.

Intestinal helminth infection transforms the CD4+ T cell composition of the skin.

Intestinal helminth parasites can alter immune responses to vaccines, other infections, allergens and autoantigens, implying effects on host immune responses in distal barrier tissues. We herein show that the skin of C57BL/6 mice infected with the strictly intestinal nematode Heligmosomoides polygyrus contain higher numbers of CD4+ T cells compared to the skin of uninfected controls. Accumulated CD4+ T cells were H. polygyrus-specific TH2 cells that skewed the skin CD4+ T cell composition towards a higher TH2/TH1 ratio which persisted after worm expulsion. Accumulation of TH2 cells in the skin was associated with increased expression of the skin-homing chemokine receptors CCR4 and CCR10 on CD4+ T cells in the blood and mesenteric lymph nodes draining the infected intestine and was abolished by FTY720 treatment during infection, indicating gut-to-skin trafficking of cells. Remarkably, skin TH2 accumulation was associated with impaired capacity to initiate IFN-γ recall responses and develop skin-resident memory cells to mycobacterial antigens, both during infection and months after deworming therapy. In conclusion, we show that infection by a strictly intestinal helminth has long-term effects on immune cell composition and local immune responses to unrelated antigens in the skin, revealing a novel process for T cell colonisation and worm-mediated immunosuppression in this organ.

Changes in obesity and lifestyle behaviours during the COVID-19 pandemic in Chinese adolescents: A longitudinal analysis from 2019 to 2020.

BACKGROUND: Since December 2019, the coronavirus disease 2019 (COVID-19) has become a global pandemic. Currently, the COVID-19 pandemic is still ongoing. What changes have taken place in the obesity and obesity-related lifestyle behaviours of adolescents during the first year of the COVID-19 pandemic? OBJECTIVE: This study aims at analysing the changes in obesity and lifestyle behaviours of Chinese adolescents before and 1 year after the outbreak of the COVID-19 pandemic, providing evidence for the global strategies to respond to the impact of the COVID-19 pandemic on adolescent obesity. METHODS: Physical examinations and student health and influencing factors questionnaires were conducted among 6047 adolescents aged 11-16 years by health professionals in Shanghai, China, before the COVID-19 pandemic (September-November of 2019) and 1 year after the outbreak of the COVID-19 pandemic (September-November of 2020). Paired χ2 tests, paired t-tests or Wilcoxon signed-rank test was used to evaluate the changes in the obesity prevalence, BMI and lifestyle behaviours from 2019 to 2020. RESULTS: 1 year after the outbreak of the COVID-19 pandemic, the obesity prevalence of Chinese adolescents rose from 14.2% to 15.4% (p < 0.01), mainly because of the increase in boys. And the average BMI increased from 20.3 to 21.2 kg/m2 (p < 0.01). Their lifestyle behaviours have also significantly changed. The mobile screen time increased from 0.25-1.50 h/day to 0.33-2.00 h/day (p < 0.01). The proportion of adolescents who participated in MVPA for ≥60 min/day on all 7 days during the past week dropped from 14.4% to 11.7% (p < 0.01). The generalized estimation equation analysis indicated that adolescents who participated in MVPA for ≥60 min/day on all 7 days had a lower likelihood of having obesity. Boys with computer time ≥2 h/day and girls with mobile screen time ≥2 h/day or TV time ≥2 h/day had a higher likelihood of having obesity. CONCLUSION: This study found that 1 year after the outbreak of the COVID-19 pandemic, the BMI and obesity prevalence of Chinese adolescents increased and obesity-related lifestyle behaviours have also changed.

Relationship between myopia and nutritional status among upper elementary students in Shanghai / 中国学校卫生

Objective@#To explore the relationship between myopia and nutritional status among upper elementary students in Shanghai.@*Methods@#A stratified cluster sampling method was used to select 5 576 fourth and fifth grade students from 16 districts in Shanghai, vision test, physical examination and questionnaire survey were administered. Two level multivariate Logistic regression and mixed linear models were used to analyze the relationship between myopia, spherical equivalent (SE) and nutritional status.@*Results@#The detection rates of overweight and obesity were 17.0%(949) and 18.7%(1 042), respectively. There was a statistical difference in the proportion of the nutritional status in boys and girls( χ 2=210.94, P <0.01), with overweight and obesity in boys higher than those of girls. The overweight boys were more likely to have myopia (univariate analysis: OR=1.23, P =0.04; multivariate analysis: OR=1.21, P =0.06) than the normal weight boy. Overweight students tended to had more negative refractive than those with normal weight in both boys and girls(multivariate analysis, boys: β =-0.19, girls: β=-0.24, P <0.05). Myopia risk and refractive power in obese students showed no statistical difference with normal weight students( P >0.05).@*Conclusion@#Overweight students have lower SE than the normal weight among upper elementary students of Shanghai, more researches are needed to confirm this finding and to provide theoretical bases for myopia prevention and control.

Alveolar macrophages rely on GM-CSF from alveolar epithelial type 2 cells before and after birth.

Programs defining tissue-resident macrophage identity depend on local environmental cues. For alveolar macrophages (AMs), these signals are provided by immune and nonimmune cells and include GM-CSF (CSF2). However, evidence to functionally link components of this intercellular cross talk remains scarce. We thus developed new transgenic mice to profile pulmonary GM-CSF expression, which we detected in both immune cells, including group 2 innate lymphoid cells and γδ T cells, as well as AT2s. AMs were unaffected by constitutive deletion of hematopoietic Csf2 and basophil depletion. Instead, AT2 lineage-specific constitutive and inducible Csf2 deletion revealed the nonredundant function of AT2-derived GM-CSF in instructing AM fate, establishing the postnatal AM compartment, and maintaining AMs in adult lungs. This AT2-AM relationship begins during embryogenesis, where nascent AT2s timely induce GM-CSF expression to support the proliferation and differentiation of fetal monocytes contemporaneously seeding the tissue, and persists into adulthood, when epithelial GM-CSF remains restricted to AT2s.

Differential sensitivity of inflammatory macrophages and alternatively activated macrophages to ferroptosis.

Acumulation of oxidized membrane lipids ultimately results in ferroptotic cell death, which can be prevented by the selenoenzyme glutathione peroxidase 4 (Gpx4). In vivo conditions promoting ferroptosis and susceptible cell types are still poorly defined. In this study, we analyzed the conditional deletion of Gpx4 in mice specifically in the myeloid cell lineages. Surprisingly, development and maintenance of LysM+ macrophages and neutrophils, as well as CD11c+ monocyte-derived macrophages and dendritic cells were unaffected in the absence of Gpx4. Gpx4-deficient macrophages mounted an unaltered proinflammatory cytokine response including IL-1ß production following stimulation with TLR ligands and activation of several inflammasomes. Accordingly, Gpx4fl/fl LysM-cre mice were protected from bacterial and protozoan infections. Despite having the capacity to differentiate to alternatively activated macrophages (AAM), these cells lacking Gpx4 triggered ferroptosis both in vitro and in vivo following IL-4 overexpression and nematode infection. Exposure to nitric oxide restored viability of Gpx4-deficient AAM, while inhibition of iNOS in proinflammatory macrophages had no effect. These data together suggest that activation cues of tissue macrophages determine sensitivity to lipid peroxidation and ferroptotic cell death.

Two New Species of Diploderma Hallowell, 1861 (Reptilia: Squamata: Agamidae) from the Hengduan Mountain Region in China and Rediscovery of D. brevicaudum (Manthey, Wolfgang, Hou, Wang, 2012).

Recent studies have highlighted the underestimated diversity of the genus Diploderma Hallowell, 1861 in the Hengduan Mountain Region in Southwest China, but much of the region remains poorly surveyed for reptile diversity. In this study we describe two new species of Diploderma from the upper Jinsha and middle Yalong River Valley, based on evaluations of morphological, genetic, and distribution data. The two new species are morphologically most similar to D. angustelinea and D. vela, but they can be diagnosed from both recognized taxa and all remaining congeners by a suite of morphological features, particularly the distinct coloration of gular spots. Additionally, both new species either render other recognized species paraphyletic or are allopatric with respect to their morphologically similar congeners. Furthermore, we rediscover D. brevicaudum in the wild for the first time, which was known from historical museum specimens only. We estimate the phylogenetic position of D. brevicaudum within the genus Diploderma based on mitochondrial genealogy, and we provide an expanded diagnosis and comparisons against closely related congeners and provide a detailed description of coloration in life based on newly collected specimens. Our discoveries of the new Diploderma species further highlight the urgent conservation needs of the currently neglected hot-dry valley ecosystems in the Hengduan Mountain Region of China.

Interrogating the Small Intestine Tuft Cell-ILC2 Circuit Using In Vivo Manipulations.

Recent findings position tuft cells as key mediators of intestinal immunity through their production of the cytokine interleukin (IL)-25 and activation of group 2 innate lymphoid cells (ILC2s). Though tuft cells are found in numerous epithelial tissues, their phenotype and function have been best characterized in the small intestine, where robust in vivo techniques have enabled the dissection of their cellular function, ontogeny, and key signaling pathways. We describe methods for the identification, quantification, and manipulation of tuft cells, focusing on analysis of ILC2s as a readout of tuft cell function. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Ex vivo analysis of small intestinal tuft cells and ILC2 by flow cytometry Alternate Protocol: Ex vivo analysis of small intestinal tuft cells and ILC2 by flow cytometry in the context of type 2 inflammation Basic Protocol 2: Ex vivo analysis of small intestinal tuft cells by imaging of intestinal Swiss roll Basic Protocol 3: Tuft-ILC2 circuit activation by oral gavage of adult Nippostrongylus brasiliensis worms Basic Protocol 4: Circuit activation by colonization with Tritrichomonas spp. Basic Protocol 5: Circuit activation by treatment with succinate in drinking water Basic Protocol 6: Circuit activation by treatment with recombinant IL-25.

Analysis of myopia related factors among primary and secondary school students in Shanghai / 中国学校卫生

Objective@#To analyze myopia related factors among students in Shanghai, to explore associated risky behaviors associated with mild, moderate, high myopia,so as to provide the evidence for the implementation of home and school combination intervention measures.@*Methods@#Six primary and secondary schools (2 primary schools, 2 middle schools and 2 high schools) were selected from each district of Shanghai. The primary schools began to investigate from the fourth grade. All the students in the selected classes participated in the vision test and questionnaire survey. Chi square test was used for categorical data analysis. The relationship between myopia and related behaviors was analyzed by multivariate Logistic analysis.@*Results@#The prevalence of visual-related risky behaviors such as short outdoor time during the day, lack of sleep, long after-school reading and writing time, poor reading and writing posture, and longtime-using mobile electronic screen was higher in girls than in boys (P<0.05), boys were more likely than girls to use computer for long time and read books/electronic screen in sunlight (P<0.05). The group with 3 hours or more than of reading and writing compared with the less than 2 hours, the OR value of mild myopia model was 1.31(1.20-1.44), moderate myopia model was 1.78(1.62-1.96), severe myopia model was 2.37(2.07-2.71). In the model of moderate and high myopia, reading and writing posture, frequency of eye relax, outdoor activity time and watching TV time were also included.@*Conclusion@#The prevalence of myopia related behaviors among primary and secondary school students is high, and there are significant gender differences among different behaviors. Students reading and writing time should be strictly controlled after school. Intervention strategies and measures should be carried out according to the characteristics of different ages and genders.

Relationship between body fat percentage and high blood pressure among junior high school students in Shanghai / 中国学校卫生

Objective@#To investigate the relationship between body fat percentage (BF%) and high blood pressure among adolescents in Shanghai, and to provide basis for early prevention and intervention of cardcovascular diseases.@*Methods@#By using stratified cluster sampling method, a total of 5 148 adolescent students in 16 schools from 16 districts of Shanghai were selected. Questionnaire survey and physical examination were performed. The bioelectrical impedance analysis (BIA) was used to measure body fat percentage. National Blood Pressure Reference for Chinese Han Children was used to define high blood pressure. And T test, chi-square test and Logistici regression were used to assess the relation between BF% with high blood pressure.@*Results@#The prevalence of high blood pressure in 5 148 junior middle school students in Shanghai was 10.98%, with girls (13.13%) higher than boys (8.99%)(χ 2=22.48, P<0.01). The average total body fat percentage of male students was (20.90±10.73)%, which decreased with age (linear trend variance is 10.04, P<0.01). The average total body fat percentage of girls was (25.14±8.03)%, which increased with age (linear trend variance is 69.23, P<0.01). After adjusted for age, diet, exercise and other influencing factors, the prevalence of hypertension showed an increasing trend with the increase of body fat percentage for both boys and girls. The risk of high blood pressure in boys with BF%≥P 90 was 12.43 times higher than that in boys with BF%<P 25(95%CI=6.98-22.14), while the risk of high blood pressure in girls with BF% ≥P 90 was 6.12 times higher than that in girls with BF%<P 25(95%CI=3.89-9.63).@*Conclusion@#There was a positive correlation between body fat percentage and high blood pressure in adolescents. The prevalence of high blood pressure increased with the increase of body fat percentage, which was more obvious in boys.

Fat Wasting Is Damaging: Role of Adipose Tissue in Cancer-Associated Cachexia.

Loss of body weight, especially loss of adipose tissue and skeletal muscle weight, characterizes cancer-associated cachexia (CAC). Clinically, therapeutic options for CAC are limited due to the complicated signaling between cancer and other organs. Recent research advances show that adipose tissues play a critical role during thermogenesis, glucose homeostasis, insulin sensitivity, and lipid metabolism. Understanding the adipocyte lipolysis, the formation of beige adipocytes, and the activation of brown adipocytes is vital for novel therapies for metabolic syndromes like CAC. The system-level crosstalk between adipose tissue and other organs involves adipocyte lipolysis, white adipose tissue browning, and secreted factors and metabolites. Novel CAC animal models and accumulating molecular signaling knowledge have provided mechanisms that may ultimately be translated into future therapeutic possibilities that benefit CAC patients. This mini review discusses the role of adipose tissue in CAC development, mechanism, and therapy.

Single-Cell RNA Sequencing of the T Helper Cell Response to House Dust Mites Defines a Distinct Gene Expression Signature in Airway Th2 Cells.

Naive CD4+ T cells differentiate into functionally diverse T helper (Th) cell subsets. Th2 cells play a pathogenic role in asthma, yet a clear picture of their transcriptional profile is lacking. We performed single-cell RNA sequencing (scRNA-seq) of T helper cells from lymph node, lung, and airways in the house dust mite (HDM) model of allergic airway disease. scRNA-seq resolved transcriptional profiles of naive CD4+ T, Th1, Th2, regulatory T (Treg) cells, and a CD4+ T cell population responsive to type I interferons. Th2 cells in the airways were enriched for transcription of many genes, including Cd200r1, Il6, Plac8, and Igfbp7, and their mRNA profile was supported by analysis of chromatin accessibility and flow cytometry. Pathways associated with lipid metabolism were enriched in Th2 cells, and experiments with inhibitors of key metabolic pathways supported roles for glucose and lipid metabolism. These findings provide insight into the differentiation of pathogenic Th2 cells in the context of allergy.

Intestinal nematode infection exacerbates experimental visceral leishmaniasis.

Leishmania donovani exposure often results in subclinical infection in immunocompetent individuals, and the factors dictating development of visceral leishmaniasis (VL) are not known. Infection with intestinal worms skew immunity towards type 2 and regulatory responses, thereby theoretically increases susceptibility to intracellular infections controlled by type 1 responses. Here we have tested how chronic infection with the intestinal nematode Heligmosomoides polygyrus affected immunity to a secondary infection with L donovani. We found that mice infected with H polygyrus displayed higher Leishmania burden in liver and spleen compared to worm-free animals. This increased infectious load was accompanied by reduced leucocyte infiltration and nos2 transcription in livers and increased il4 and il10 transcription in spleens. Collectively, these data show that chronic infection with intestinal nematodes skew immune responses in a way that may favour development of VL.

Urinary angiotensinogen: an indicator of active antineutrophil cytoplasmic antibody-associated glomerulonephritis.

BACKGROUND: One of the major challenges in improving the management of antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) is the lack of a disease-specific indicator for histological lesions and disease activity. Here we tested the utility of urinary angiotensinogen (UAGT) as a biomarker of renal disease activity in ANCA-GN. METHODS: A prospective, two-stage cohort study was performed in ANCA-GN patients. In Stage I, UAGT was measured at the time of renal biopsy in 69 patients from two centers (test set) and 25 patients from two other centers (validation set). In Stage II, UAGT was monitored in 50 subjects in the test set for 24 months. RESULTS: In Stage I, UAGT significantly increased in ANCA-GN patients, correlating well with cellular crescents formation and active interstitial inflammation. Patients with crescentic ANCA-GN exhibited the highest UAGT compared with other histopathological classes of ANCA-GN. After multivariable adjustment, the highest quartile of UAGT, compared with the lowest quartile, associated with a 6-fold increased risk of crescentic ANCA-GN. For predicting crescentic ANCA-GN, UAGT [area under the receiver operating characteristics curve (AUC) = 0.88] outperformed albuminuria (AUC = 0.73) and estimated glomerular filtration rate (AUC = 0.69). UAGT improved the performance of those clinical markers in diagnosing crescentic ANCA-GN (P < 0.034), suggesting a role of UAGT in identifying active crescentic ANCA-GN. In Stage II, UAGT decreased after immunotherapy and increased at the time of renal relapse during the 2-year follow-up, suggesting the usefulness of UAGT to monitor disease activity over time. CONCLUSIONS: These results suggest the potential use of UAGT for assessing disease activity and renal relapse in ANCA-GN.

Intervention effect of hand washing behavior in primary and secondary schools in Shanghai by non-participatory observation / 中国学校卫生

Objective@#To assess the changes of students’ hand washing behaviors after implementing comprehensive interventions, and to provide the reference for hand-washing promotion among students.@*Methods@#The implementation of comprehensive intervention projects had been carried out in three aspects: hardware transformation, system establishment, health management and health education. A randomized controlled trial method was used to select each one primary and secondary school in 2016 from 17 districts in Shanghai, and 17 intervention schools and 17 control schools were taken as object. Non-participant observation was used for students’ hand washing behaviors for 4 times during May, 2016 to May, 2017. Descriptive analysis and chi square test were used to analyze the data.@*Results@#Compared with the control group, the hand washing rate of the intervention group was lower than that of the control group at baseline. The intervention group has got a higher rate than that of the control group in the evaluation of 1, the assessment 2 and the assessment 3 after intervention. The difference was statistically significant(χ2=7.70, 24.23, 38.88, 21.71, P<0.05). Compared with the control group, the hand washing rate of the intervention group after class was lower than that of the control group. After the intervention, the rate of the intervention group was higher than that of the control group in the evaluation 1, the assessment 2 and the assessment 3 after the intervention. The difference was statistically significant (χ2=8.52, 33.79, 54.64, 13.99, P<0.05). Compared with the control group, there was no difference between the baseline intervention group and the control group before meals. The intervention group after intervention was higher than the control group in the evaluation of 1, evaluation 2 and evaluation 3. The difference was statistically significant (χ2=45.01, 42.19, 27.82, P<0.05).@*Conclusion@#After comprehensive intervention, the effect was significant under different temperature conditions, and the effect of intervention lasted for one year.

Effect evaluation on physical activity intervention for primary school students in Shanghai / 中国学校卫生

Objective@#To evaluate the effects of physical activity interventions based on social ecology model, and to explore promising approach for increasing physical activity of students in large cities.@*Methods@#A quasi-experimental design with parallel control was implemented. Students from grade 4 in 20 primary schools in 3 districts of Shanghai were recruited. Based on social ecology model, physical activity interventions were carried out in three levels: personal, social-and physical environment. The interventions lasted for 6 months. Questionnaires, physical examinations and physical fitness tests were carried out. Rank sum test, chi-square test and logistic stepwise regression was used to analyze the intervention effects.@*Results@#In the intervention group, the proportion of students who favored physical activity increased from 47.9% to 50.7%. Time spent in moderate to vigorous intensity physical activity (MVPA) increased from 64 min/d to 70 min/d, mainly during the weekend. The interventions showed significant effects, especially for girls. In the intervention group, the proportion of students spent 1 h/d in MVPA increased from 53.7% to 57.7%(χ2=4.95, P<0.05). Multivariate analysis showed that after intervention, the proportion of students spent more than 1 h/d in MVPA in the intervention group was higher than that in the control group (OR=1.22, 95%CI=1.02-1.48, P=0.03).@*Conclusion@#Physical activity interventions based on social ecology model can increase uptake of physical activity among school students.

Atrophy of skin-draining lymph nodes predisposes for impaired immune responses to secondary infection in mice with chronic intestinal nematode infection.

Intestinal nematodes suppress immune responses in the context of allergy, gut inflammation, secondary infection and vaccination. Several mechanisms have been proposed for this suppression including alterations in Th2 cell differentiation and increased Treg cell suppressive function. In this study, we show that chronic nematode infection leads to reduced peripheral responses to vaccination because of a generalized reduction in the available responsive lymphocyte pool. We found that superficial skin-draining lymph nodes (LNs) in mice that are chronically infected with the intestinal nematode Heligmosomides polygyrus, do not reach the same cellularity as worm-free mice upon subsequent BCG infection in the skin. B cells and T cells, all declined in skin-draining LN of H. polygyrus-infected mice, resulting in LNs atrophy and altered lymphocyte composition. Importantly, anti-helminthic treatment improved lymphocyte numbers in skin-draining LN, indicating that time after de-worming is critical to regain full-scale LN cellularity. De-worming, and time for the skin LN to recover cellularity, also mended responses to Bacille Calmette-Guerin (BCG) in the LN draining the footpad injection site. Thus, our findings show that chronic nematode infection leads to a paucity of lymphocytes in peripheral lymph nodes, which acts to reduce the efficacy of immune responses at these sites.

PPAR-γ promotes type 2 immune responses in allergy and nematode infection.

A hallmark of immunity to worm infections and many allergies is a strong type 2 immune response. This is characterized by the production of cytokines interleukin-5 (IL-5) and IL-13 by adaptive T helper 2 (TH2) cells and/or type 2 innate lymphoid cells. Peroxisome proliferator activated receptor-γ (PPAR-γ) is typically regarded as an anti-inflammatory factor. We report that TH2 cells express high levels of PPAR-γ in response to the allergen house dust mite and after infection with the parasite Heligmosomoides polygyrus Mice lacking PPAR-γ in T cells failed to effectively differentiate into IL-5- and IL-13-secreting cells and, hence, did not develop TH2 cell-associated pathologies, including goblet cell metaplasia and eosinophilia, in response to allergen challenge. Furthermore, these mice could not mount protective immune responses to nematode infection. In addition, mice lacking PPAR-γ in T cells had greatly reduced frequencies of TH2 cells in visceral adipose tissue. Mechanistically, PPAR-γ appeared to promote the expression of the IL-33 receptor on the surface of TH2 cells. These results pinpoint PPAR-γ as a factor that drives type 2 responses in allergy, worm infection, and visceral adipose tissue.