Search

Background: 4‐1BB (CD137), a member of the inducible tumor necrosis factor receptor (TNFR) family, is expressed on regulatory T (Treg) cells and regulates Treg cells to control allergic inflammation. Pam3CSK4, a synthetic TLR2 ligand that can expand CD8+ Treg function, is a promising adjuvant for allergen immunotherapy (IT). We examined whether Dermatophagoides pteronyssinus (Der p) IT and Pam3CSK4 could enhance CD8+ CD25+ CD137+ Treg suppressive function to decrease nasal nitric oxide (nNO) levels. Methods: Nasal symptom scores, nNO levels, PBMCs, and inferior turbinate biopsies were obtained from 40 mite‐sensitive perennial allergic rhinitis (PAR) patients before and after one year of Der p IT and 30 non‐allergic control subjects. CD137 expression on CD8+ CD25+ T cells and suppressive function of CD8+ CD25+ CD137+ Tregs was measured using flow cytometry. Cytokine levels were analyzed by ELISA. Inducible nitric oxide synthase production by nasal epithelial cells after co‐culturing with CD8+ CD25+ CD137+ T cells was analyzed by Western blotting. Results: Der p IT improved nasal symptom scores, decreased nNO levels, and increased CD137 expression on CD8+ T cells in PBMCs and nasal mucosa. Pam3CSK4 expanded the CD8+ CD25+ CD137+ population in PBMCs. Pam3CSK4‐stimulated CD8+ CD25+ CD137+ Tregs induced IL‐10 and TGF‐β and suppressed CD4+ CD25‐ T‐cell proliferation mainly by cell contact inhibition. CD8+ CD25+ CD137+ Tregs cultured with nasal epithelial cells suppressed Der p 2–induced iNOS production. Silencing CD137 in sorted CD8+ CD25+ T cells decreased Pam3CSK4‐activated Foxp3 expression. Conclusion: Der p IT expanded CD8+ CD25+ CD137+ Tregs and decreased nNO levels. Induced CD137 expression on CD8+ CD25+ Tregs by Pam3CSK4 stimulation may help suppress allergic inflammation during IT. [ABSTRACT FROM AUTHOR]

Background: Exhaled nitric oxide concentration (FENO) is a marker of airway inflammation. This study aimed to evaluate the association of air pollution exposure with FENO levels and asthma prevalence with respiratory symptoms in school children., Methods: We analyzed 4736 school children who reside in six townships near industrial areas in central Taiwan. We evaluated asthmatic symptoms, FENO, and conducted the environmental questionnaire. The personal exposure of PM 2.5 , NO, and SO 2 was estimated using land-use regression models data on children's school and home addresses., Results: Annual exposure to PM 2.5 was associated with increased odds of physician-diagnosed asthma (OR = 1.595), exercise-induced wheezing (OR = 1.726), itchy eyes (OR = 1.417), and current nasal problems (OR = 1.334) (P < 0.05). FENO levels in the absence of infection were positively correlated with age, previous wheezing, allergic rhinitis, atopic eczema, near the road, and for children with high exposure to PM 2.5 (P < 0.05). An increase of 1 μg/m 3 PM 2.5 exposure was significantly associated with a 1.0% increase in FENO levels for children after adjusting for potential confounding variables, including exposures to NO and SO 2 ., Conclusions: Long-term exposures to PM 2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children., Impact: Annual exposure to PM 2.5 was associated with increased odds of physician-diagnosed asthma and nasal problems and itchy eyes. Long-term exposures to PM2.5 were significantly associated with FENO levels after adjusting for potential confounding variables. This is first study to assess the association between FENO levels and long-term air pollution exposures in children near coal-based power plants. An increase of 1 μg/m 3 annual PM 2.5 exposure was significantly associated with a 1.0% increase in FENO levels. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: The interplay of air pollution and urban greenness on hypertension (HTN) is not fully understood., Methods: We conducted a cross-sectional study to explore the role of greenness and PM 2.5 on HTN for 40,375 adult residents in the New Taipei City, Taiwan. Normalized Difference Vegetation Index (NDVI) defined greenness and land use regression derived exposures of PM 2.5 were used to calculate odds ratios (ORs) of HTN in logistic regression models and common OR of normal to stage 3 HTN in ordinal logistic regression models. Linear regression model was used to evaluate the association between NDVI and blood pressures, including systolic (SBP), diastolic (DBP) and mean (MBP) pressures. The mediation and moderation analysis were used to assess the mediation and moderation effect of PM 2.5 on the association between greenness and SBP., Results: We found 37.3%, 21.4%, 8.2% and 2.7% of prehypertension and stage 1-3 hypertensions, respectively, for our study participants with annual PM 2.5 exposures of 10.96-43.59 μg/m 3 living in an urban environment with NDVI within 500 m buffer ranging from -0.22 to 0.26. The ORs of HTN were 0.744 (95% CI: 0.698-0.793) for NDVI (quartile 4 vs. quartile 1) and 1.048 (1.012-1.085) for each IQR (8.69 μg/m 3 ) increase in PM 2.5 , respectively. The common OR of the higher level of 5 categories of BP was 1.1310 (1.241-1.383). With each IQR increase of NDVI (0.03), we found SBP, DBP and MBP were decreased by 0.78 mm Hg (-0.93-0.64), 0.52 mm Hg (-0.62-0.43) and 0.61 mm Hg (-0.71-0.51), respectively, in linear regression models. Stratified analysis found greenness effect was more prominent for people who are younger, female, never smoking, and without chronic diseases. PM 2.5 is moderated rather than mediated the association between greenness and SBP., Conclusions: Greenness was associated with lower prevalence of prehypertension and all stages of HTN and this relationship was moderated by PM 2.5 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Pam3CSK4, a synthetic TLR2 ligand, has been shown to expand CD4+ regulatory T cells (Treg cells). Less is known about the function of CD8+ Treg cells than about the function of CD4+ Treg cells generated during allergen-specific immunotherapy (IT). This study investigated whether Dermatophagoides pteronyssinus-specific IT could expand the CD8+CD25+Foxp3+ Treg population and whether Pam3CSK4 could enhance the Treg population. PBMCs were isolated from healthy control subjects and from mite-sensitive asthmatic patients during IT at three specific times: before IT and 6 mo and 1 y after the maximum-tolerated dose. This study was performed without a placebo-controlled group. D. pteronyssinus-specific IT induced a significant increase in CD8+Foxp3+ Treg cells expressing intracellular IL-10 and granzyme B. Costimulation of PBMCs with Pam3CSK4 and D. pteronyssinus 2 expanded the CD8+CD25+Foxp3+ Treg population and inhibited D. pteronyssinus 2-induced IL-4 production. Pam3CSK4-treated CD8+CD25+ Treg cells directly suppressed CD4+ T cell proliferation by cell-contact inhibition. TUNEL revealed that CD8+CD25+ Treg cells, but not CD4+CD25+ Treg cells, directly induced CD4+CD45ROhi+ apoptosis. Our results provide direct evidence that Pam3CSK4 induces an immunomodulatory effect by inducing CD8+ Treg cells; therefore, it may be a good adjuvant for the treatment of mite allergies.

The pathogenesis of minimal change nephrotic syndrome (MCNS) is still not clear. Several studies indicate that MCNS is a systemic disorder of cell-mediated immunity. IL-12 is a pleiotropic cytokine that is produced primarily by macrophage and plays a primary role in the induction of Th1-mediated immunity. The purpose of this study is to explore the relationship of in vivo IL-12 levels in both sera and urine, and in vitro IL-12 production in stable or nephrotic clinical condition patients with MCNS. In vitro IL-12 production was detected from LPS-stimulated peripheral blood mononuclear cells (PBMNCs) of 20 MCNS patients during nephrotic and remission stages, levels of sera and urinary IL-12 were measured by commercially available ELISA kits (R & D Systems, Minneapolis). The results showed sera IL-12 levels and LPS-stimulated IL-12 productions for PBMNCs were significantly increased as compared with those of normal controls and in remission stage. However, there was also statistical difference of urinary IL-12 levels among MCNS patients during nephrotic and remission stage and controls. This study demonstrates a correlation between in vitro IL-12 release by PBMNCs and in vivo sera IL-12 level from MCNS patients as well as correlation with disease activity. The study contributes to the understanding of the pathogenesis of MCNS.