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Browsing by Author "Qi, Rong"
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Item BATF Regulates T Regulatory Cell Functional Specification and Fitness of Triglyceride Metabolism in Restraining Allergic Responses(American Association of Immunologists, 2021) Xu, Chengxian; Fu, Yongyao; Liu, Sheng; Trittipo, Jack; Lu, Xiaoyu; Qi, Rong; Du, Hong; Yan, Cong; Zhang, Chi; Wan, Jun; Kaplan, Mark H.; Yang, Kai; Pediatrics, School of MedicinePreserving appropriate function and metabolism in regulatory T (Treg) cells is crucial for controlling immune tolerance and inflammatory responses. Yet how Treg cells coordinate cellular metabolic programs to support their functional specification remains elusive. In this study, we report that BATF couples the TH2-suppressive function and triglyceride (TG) metabolism in Treg cells for controlling allergic airway inflammation and IgE responses. Mice with Treg-specific ablation of BATF developed an inflammatory disorder characterized by TH2-type dominant responses and were predisposed to house dust mite-induced airway inflammation. Loss of BATF enabled Treg cells to acquire TH2 cell-like characteristics. Moreover, BATF-deficient Treg cells displayed elevated levels of cellular TGs, and repressing or elevating TGs, respectively, restored or exacerbated their defects. Mechanistically, TCR/CD28 costimulation enhanced expression and function of BATF, which sustained IRF4 activity to preserve Treg cell functionality. Thus, our studies reveal that BATF links Treg cell functional specification and fitness of cellular TGs to control allergic responses, and suggest that therapeutic targeting of TG metabolism could be used for the treatment of allergic disease.Item The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity(Elsevier, 2021-06) Xu, Chengxian; Sun, Shaogang; Johnson, Travis; Qi, Rong; Zhang, Siyuan; Zhang, Jie; Yang, Kai; Pediatrics, School of MedicineT regulatory (Treg) cells are crucial to maintain immune tolerance and repress antitumor immunity, but the mechanisms governing their cellular redox homeostasis remain elusive. We report that glutathione peroxidase 4 (Gpx4) prevents Treg cells from lipid peroxidation and ferroptosis in regulating immune homeostasis and antitumor immunity. Treg-specific deletion of Gpx4 impairs immune homeostasis without substantially affecting survival of Treg cells at steady state. Loss of Gpx4 results in excessive accumulation of lipid peroxides and ferroptosis of Treg cells upon T cell receptor (TCR)/CD28 co-stimulation. Neutralization of lipid peroxides and blockade of iron availability rescue ferroptosis of Gpx4-deficient Treg cells. Moreover, Gpx4-deficient Treg cells elevate generation of mitochondrial superoxide and production of interleukin-1β (IL-1β) that facilitates T helper 17 (TH17) responses. Furthermore, Treg-specific ablation of Gpx4 represses tumor growth and concomitantly potentiates antitumor immunity. Our studies establish a crucial role for Gpx4 in protecting activated Treg cells from lipid peroxidation and ferroptosis and offer a potential therapeutic strategy to improve cancer treatment.Item The obesity epidemic in children: Latino children are disproportionately affected at younger ages(Elsevier, 2015-03) Liu, Gilbert C.; Hannon, Tamara; Qi, Rong; Downs, Stephen M.; Marrero, David G.; Department of Medicine, IU School of MedicineBackground and objectives National surveillance clearly illustrates that U.S. children are becoming increasingly overweight. However, the timing of the onset of childhood overweight has not been well-described. Patients and methods An accelerated failure time (AFT) model was used to describe the emergence of overweight based on a 12-year collection of height and weight data of over 40,000 children. Race, sex, insurance status and their interactions were specifically examined as predictors of earlier onset of overweight. The outcome of interest was an estimate of the age at which the model predicted that a subgroup would attain a 20% prevalence of overweight. Results The three-way interaction of race, sex, and insurance status was a significant predictor of onset of overweight. The model estimated that the publicly insured Latino male subgroup had the earliest onset of overweight, attaining a prevalence of 20% overweight by 4.3 years of age. The emergence of overweight in Latino subjects was significantly earlier than that for black or white subjects, irrespective of sex or insurance status. Conclusion Regardless of sex or insurance status, overweight emerges at significantly younger ages in Latino children when compared to black and white children. Substantial numbers of Latino male children are predicted to develop overweight at preschool ages. Obesity prevention may need to be directed toward parents or children well before children enter grade-school.Item Predicting pharmacotherapeutic outcomes for type 2 diabetes: An evaluation of three approaches to leveraging electronic health record data from multiple sources(Elsevier, 2022-05) Tarumi, Shinji; Takeuchi, Wataru; Qi, Rong; Ning, Xia; Ruppert, Laura; Ban, Hideyuki; Robertson, Daniel H.; Schleyer, Titus; Kawamoto, Kensaku; Medicine, School of MedicineElectronic health record (EHR) data are increasingly used to develop prediction models to support clinical care, including the care of patients with common chronic conditions. A key challenge for individual healthcare systems in developing such models is that they may not be able to achieve the desired degree of robustness using only their own data. A potential solution—combining data from multiple sources—faces barriers such as the need for data normalization and concerns about sharing patient information across institutions. To address these challenges, we evaluated three alternative approaches to using EHR data from multiple healthcare systems in predicting the outcome of pharmacotherapy for type 2 diabetes mellitus (T2DM). Two of the three approaches, named Selecting Better (SB) and Weighted Average (WA), allowed the data to remain within institutional boundaries by using pre-built prediction models; the third, named Combining Data (CD), aggregated raw patient data into a single dataset. The prediction performance and prediction coverage of the resulting models were compared to single-institution models to help judge the relative value of adding external data and to determine the best method to generate optimal models for clinical decision support. The results showed that models using WA and CD achieved higher prediction performance than single-institution models for common treatment patterns. CD outperformed the other two approaches in prediction coverage, which we defined as the number of treatment patterns predicted with an Area Under Curve of 0.70 or more. We concluded that 1) WA is an effective option for improving prediction performance for common treatment patterns when data cannot be shared across institutional boundaries and 2) CD is the most effective approach when such sharing is possible, especially for increasing the range of treatment patterns that can be predicted to support clinical decision making.Item Utilization of electronic health records for the assessment of adiponectin receptor autoantibodies during the progression of cardio-metabolic comorbidities(Probiologists, 2020) Pugia, Michael J.; Pradhan, Meeta; Qi, Rong; Eastes, Doreen L.; Vorsilak, Anna; Mills, Bradley J.; Baird, Zane; Wijeratne, Aruna; McAhren, Scott M.; Mosley, Amber; Shekhar, Anantha; Robertson, Daniel H.; Biochemistry and Molecular Biology, School of MedicineBackground: Diabetes is a complex, multi-symptomatic disease whose complications drives increases in healthcare costs as the diabetes prevalence grows rapidly world-wide. Real-world electronic health records (EHRs) coupled with patient biospecimens, biological understanding, and technologies can characterize emerging diagnostic autoimmune markers resulting from proteomic discoveries. Methods: Circulating autoantibodies for C‑terminal fragments of adiponectin receptor 1 (IgG-CTF) were measured by immunoassay to establish the reference range using midpoint samples from 1862 participants in a 20-year observational study of type 2 diabetes and cardiovascular arterial disease (CVAD) conducted by the Fairbanks Institute. The White Blood Cell elastase activity in these patients was assessed using immunoassays for Bikunin and Uristatin. Participants were assigned to four cohorts (healthy, T2D, CV, CV+T2D) based on analysis of their EHRs and the diagnostic biomarkers values and patient status were assessed ten-years post-sample. Results: The IgG-CTF reference range was determined to be 75–821 ng/mL and IgG-CTF out-ofrange values did not predict cohort or comorbidity as determined from the EHRs at 10 years after sample collection nor did IgG-CTF demonstrate a significant risk for comorbidity or death. Many patients at sample collection time had other conditions (hypertension, hyperlipidemia, or other risk factors) of which only hypertension, Uristatin and Bikunin values correlated with increased risk of developing additional comorbidities (odds ratio 2.58–13.11, P<0.05). Conclusions: This study confirms that retrospective analysis of biorepositories coupled with EHRs can establish reference ranges for novel autoimmune diagnostic markers and provide insights into prediction of specific health outcomes and correlations to other markers.