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B Cell Mechanisms of Tolerance Following Infant Peanut Consumption

婴儿食用花生后 B 细胞的耐受机制

基本信息

批准号：
10190828
负责人：
Adora A Lin
金额：
$ 17.94万
依托单位：
CHILDREN'S RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10190828
关键词：
3 year old 5 year old Address Age-Months Allergen Immunotherapy Allergic Allergy to eggs Allergy to peanuts Anaphylaxis Antibody-Producing Cells Area Atopic Dermatitis B-Lymphocyte Subsets B-Lymphocytes Binding Bioinformatics Biological Markers Biology Biometry Breastfed infant Cattle Cellular biology Cessation of life Child Clinical Clinical Research Consumption Data Developed Countries Development Development Plans Diagnosis Diagnostic Procedure Down-Regulation Environment Evaluation Family Food Food Hypersensitivity Frequencies Funding Future Gene Expression Gene Expression Profile Genes Genetic Transcription Goals Health Care Costs Hypersensitivity IgE IgG4 Immune Immunoglobulin Class Switching Immunoglobulins Immunologics Immunologist Immunology Immunotherapeutic agent Infant Institution Interleukin-10 Intervention Investigation Knowledge Learning Life Measurement Measures Mediating Medical Medical center Mentors Milk Monitor Oral Pathogenesis Pathway interactions Patients Peripheral Blood Mononuclear Cell Physicians Positioning Attribute Prevalence Prevention Production Quality of life Research Research Design Research Personnel Research Project Grants Resources Risk Role Sampling Scientist Secure Serum Shapes Systems Biology T cell therapy Therapeutic Time Training United States National Institutes of Health Universities Washington atopy base career career development critical period cytokine design differential expression egg experience feasibility research food challenge high risk high risk infant improved infancy insight interleukin-10 receptor next generation sequencing novel novel diagnostics novel marker oral immunotherapy psychosocial receptor expression response skills training opportunity transcriptome transcriptome sequencing transcriptomics

项目摘要

PROJECT SUMMARY/ABSTRACT This proposal details a 5-year plan to provide the candidate, Dr. Adora Lin, with the knowledge and expertise to become an independent investigator in the field of Allergy and Immunology. The proposed research is a novel investigation of the role of B cells in the development of peanut allergy versus tolerance in infants deemed at high risk for peanut allergy. Although studies suggest that early introduction of peanut to high-risk infants can influence the development of peanut allergy versus tolerance, with accompanying changes in peanut-specific immunoglobulin levels, the biology of the B cells producing these immunoglobulins and regulatory mechanisms mediating these changes are unknown. The candidate will evaluate the B cell response to IL-10, regulatory B cells (B regs), and the B cell transcriptome in samples collected from infants at high risk for peanut allergy, both prior to peanut introduction and during peanut consumption or avoidance. The specific aims of the project are: 1) To determine whether increased B cell responsiveness to IL-10 and increased B reg frequency and function identify infants at high risk for peanut allergy who tolerate peanut, 2) To evaluate whether regular peanut consumption augments B cell responsiveness to IL-10 and B reg frequency and function in infants at high risk for peanut allergy, and 3) To define the B cell transcription signature associated with peanut tolerance. Findings from this research will address significant gaps in our knowledge regarding the impact of B cells during the critical early period that shapes food allergy versus tolerance. These findings may be leveraged into future studies evaluating novel biomarkers for distinguishing food allergy versus tolerance, new diagnostic methods, improved monitoring of allergen immunotherapy, and B cell-targeted interventions for food allergy. This research will also provide new insights into B cell biology, B regs, and the B cell transcriptome during infancy. The candidate has assembled an outstanding team of NIH- funded mentors, who have committed their time, expertise, and resources to facilitate the candidate's research and career goals. Dr. Bollard is a world-renowned translational immunologist and expert in adoptive T cell therapies. Dr. Guerrerio is a leading expert in food allergy pathogenesis. Dr. Freishtat has extensive expertise in transcriptomics and systems biology. The candidate will participate in coursework designed to provide her with further skills in advanced biostatistics, clinical study design, next-generation sequencing, bioinformatics, and various areas of professional development. She will benefit from an ideal scientific, educational, and clinical environment provided by her primary institution, Children's National Medical Center, enhanced by training opportunities at the George Washington University and National Institutes of Health. In summary, this proposal describes a relevant and feasible research project and career development plan that will position the candidate to secure independent NIH funding and establish herself in a niche area of academic food allergy.

项目总结/文摘