Regulatory T Cells in Gestation and Childhood Allergic Disease

妊娠期和儿童过敏性疾病中的调节性 T 细胞

• 批准号: 7743029
• 负责人: Ganesa Rebecca Wegienka
• 金额: $ 11.25万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-15 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7743029
• 关键词: 2 year old; Allergic; Allergic Disease; Allogenic; Area; Birth; Birth Order; Blood; Cells; Child; Childhood; Cohort Studies; Data; Development; Endotoxins; Epidemic; Epidemiologic Studies; Epidemiology; Fetus; Fever; Funding; Future; Health system; Hospitals; Human; Hygiene; Hypersensitivity; IgE; Immune Tolerance; Immune system; Immunity; Infection; Interferons; Interleukin-10; Interleukin-4; Internet; Live Birth; Longitudinal Studies; Mentored Research Scientist Development Award; Morbidity - disease rate; Mothers; Mus; Outcome; Outcomes Research; Patient Self-Report; Pattern; Perinatal Exposure; Postpartum Period; Pregnancy; Pregnancy Histories; Pregnancy Interval; Pregnant Women; Process; Recruitment Activity; Regulatory T-Lymphocyte; Research; Research Personnel; Research Training; Risk; Role; Siblings; Skin; Smoking; Testing; Tetanus; Th2 Cells; Training Programs; Transference; Umbilical Cord Blood; airborne allergen; allergic response; cohort; cytokine; disorder risk; early childhood; early life exposure; fetal; food allergen; in utero; infancy; mortality; pet animal; prenatal; prevent; programs; reproductive epidemiology; response; skills; transmission process

DESCRIPTION (provided by applicant): This Mentored Research Scientist Development Award in Epidemiology and Outcomes Research (K01) will allow me to transition from reproductive epidemiology to childhood allergic disease (CAD) epidemiology research under the guidance of a successful CAD epidemiology research group. Through this proposed research and training program, I will develop the skills needed to become an independent researcher in the field of CAD. CAD are a growing epidemic and are associated with mortality and considerable morbidity. Thirty percent of cases have been attributed to the children's birth order. But, the underlying mechanism cannot be explained by the hygiene hypothesis, because there is little evidence of covariation of infection rates with birth order. Allergic status has been characterized by the T-helper1/T-helper2 ratio (Th1/Th2 ratio) skewed toward a Th2 cell-cytokine predominance, with the role of Th1 in the allergic response not yet defined. Pregnancy is assumed to be a Th2 dominant process. Thus pregnancy is likely a critical component in the causal web of CAD. T regulatory cells (Tregs), which suppress allogenic responses against the fetus in mice and humans, increase in successful pregnancy and decrease, but remain above pre-pregnancy levels, during the postpartum. Research has indicated that Tregs can control both Th1 and Th2 responses. Although a mode of tolerance transference from mother to fetus has not yet been identified, this could explain the observed association between birth order and subsequent CAD risk. Hence the question: what is the role of maternal Tregs during pregnancy in the risk of CAD? As part of an ongoing NIH-funded study, a birth cohort is being recruited for longitudinal study in the Detroit area to study early life exposures in the development of CAD. Using a subset of 225 mother-child pairs from this cohort, we will study the following hypotheses (Tregs: CD4+CD25+FOXP3+ and CD4+CD25+CTLA4+). Our hypotheses are: 1) More prior live births and shorter pregnancy intervals will be predictive of: a. Higher maternal Tregs during pregnancy and at 1, 6 and 12 months postpartum; b. Lower maternal prenatal IgE; and 2) Higher maternal Tregs during pregnancy are predictive of: a. Higher Tregs in their child's blood at delivery (cord), 6 and 12 months and 2 years; b. Lower IgE in their child's blood at delivery (cord), 6 and 12 months and 2 years; c. Reduced risk of their child having a positive skin prick test for common aeroallergens and food allergens at age 2 years.

描述（由申请人提供）：这个指导研究科学家发展奖流行病学和成果研究（K 01）将使我从生殖流行病学过渡到儿童过敏性疾病（CAD）流行病学研究的指导下，一个成功的CAD流行病学研究小组。通过这项研究和培训计划，我将发展成为CAD领域独立研究人员所需的技能。CAD是一种日益增长的流行病，与死亡率和相当高的发病率相关。30%的病例归因于孩子的出生顺序。但是，基本的机制不能用卫生假说来解释，因为几乎没有证据表明感染率与出生顺序存在协变。过敏状态的特征在于T辅助细胞1/T辅助细胞2比率（Th 1/Th 2比率）偏向于Th 2细胞-细胞因子优势，而Th 1在过敏反应中的作用尚未确定。妊娠被认为是Th 2占主导地位的过程。因此，妊娠可能是CAD因果网络中的一个关键组成部分。调节性T细胞（TCRs）抑制小鼠和人类对胎儿的同种异体反应，在成功怀孕时增加，在产后减少，但仍高于妊娠前水平。研究表明，Th 2可以控制Th 1和Th 2反应。虽然尚未确定从母亲到胎儿的耐受性转移模式，但这可以解释出生顺序与随后的CAD风险之间观察到的关联。因此，问题是：妊娠期间母体TdR在CAD风险中的作用是什么？作为NIH资助的一项正在进行的研究的一部分，正在招募一个出生队列进行底特律地区的纵向研究，以研究CAD发展中的早期生活暴露。使用来自该队列的225对母子对的子集，我们将研究以下假设（T细胞：CD 4 + CD 25 + FOXP 3+和CD 4 + CD 25 + CTLA 4+）。我们的假设是：1）更多的活产和更短的怀孕间隔将预测：a。妊娠期间和产后1、6和12个月时母体TdR较高; B.较低的母体产前IgE;和2）妊娠期间较高的母体TIgE预测：a.分娩时（脐带血）、6个月和12个月以及2岁时婴儿血液中的TdR较高; B.在分娩时（脐带血）、6个月和12个月以及2岁时，其孩子血液中的IgE较低; c.降低孩子在2岁时对常见空气过敏原和食物过敏原进行阳性皮肤点刺试验的风险。