Erythroid cell modulation of T cell function

红细胞对 T 细胞功能的调节

• 批准号: 8969951
• 负责人: ELIZABETH A. BONNEY
• 金额: $ 23.06万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8969951
• 关键词: Adult; Affect; Age; Allergic Disease; Antigens; Architecture; Asthma; Autoimmune Diseases; Biological Markers; CD4 Positive T Lymphocytes; Cell Lineage; Cell physiology; Cells; Cellular biology; Child; Child health care; Coculture Techniques; Communicable Diseases; Contracts; Development; Diagnosis; Diagnostic; Employee Strikes; Environment; Erythrocytes; Erythroid Cells; Event; Exposure to; Generations; Growth Factor; Health; Hematopoietic; Hematopoietic stem cells; Homeostasis; Human; Immune; Immune System Diseases; Immune response; Immune system; Immunity; Immunization; In Vitro; Infant; Infant Health; Infection; Infectious Disease Immunology; Inflammatory; Influenza; Interleukin-4; Interleukin-6; Interleukin-7; Investigation; Laboratories; Lead; Life; Lymphoid; Malignant Childhood Neoplasm; Methods; Modeling; Molecular; Mus; Neonatal; Newborn Infant; Organ; Phenotype; Physicians; Play; Population; Predisposition; Pregnancy; Premature Infant; Production; Protocols documentation; Regulation; Research Personnel; Resources; Role; Scientist; Second Pregnancy Trimester; Spleen; Sum; System; Systems Development; T cell response; T-Cell Development; T-Cell Proliferation; T-Lymphocyte; Testing; Thinking; Third Pregnancy Trimester; Time; Vermont; Work; adaptive immunity; base; cell type; cytokine; experience; falls; fetal; granulocyte; in vivo; lymph nodes; member; method development; neonatal human; neonate; novel; organ growth; premature; receptor; receptor expression; response; trafficking

DESCRIPTION (provided by applicant): There is critical need for enhanced understanding of the developing immune system in order to increase the health of children and the adults they become. Infectious diseases more harshly affect the newly born, the prematurely born, and the young under the age of five. Young children can be affected by inappropriate inflammatory or adaptive immune responses to environmental antigens and this may predispose them to allergic or autoimmune disease. Finally, the altered development of the early immune system plays a role in childhood cancer. Recent thinking is that the neonatal immune system is a sum of interactions between `fetal' and `adult' components, however, little is known about how these `systems' interact, transition, or affect overall immunity in neonates. We have studied the mouse immune system between 1-3 weeks of life, as many aspects model the immune system of mid-late gestational and newborn humans. We have observed striking changes during this time frame. For example, before T cells fully populate the spleen, a unique erythrocyte lineage (EL) cell expands to a peak on days 6 of life, is the dominant population in the spleen for several days and then contracts to near adult levels by day 21 of life. The fall in EL is concomitant with rise in spleen T cells. Co-culture between neonatal EL and adult CD4 T cells led to increased EL production of IL-6 and in turn was associated with decreased γIFN and increased IL-4 production by CD4 T cells. These observations and existing evidence suggesting that both EL and T cells respond to the growth factor IL-7 lead us to the novel overall hypothesis that in vivo expansion and contraction of EL as well as expansion of T cells in the neonatal spleen is regulated by competition for IL-7 and that activation of EL in this context increases EL-produced IL-6 which in turn directly supports "Th-2" differentiation in vivo during this period of neonatal life. The work proposed in this R21 application takes advantage of unique genetically manipulated mice, the experience of an expert in the role of IL-6 in the regulation of immune responses and a laboratory experienced in both the study of T cell homeostasis and maternal and neonatal immunity. The results are expected to inform development of methods to diagnose immune dysfunction in preterm and term human infants, and guide investigation of methods to enhance protective and modulate inappropriate immunity in the neonatal period.

描述（由适用提供）：为了提高他们成为儿童和成年人的健康状况，至关重要的是增强对发展中的免疫系统的了解。传染病更加有害影响新生，过早出生和五岁以下的年轻人。幼儿可能会受到对环境抗原的不当炎症或适应性免疫的影响，这可能会使他们患过过敏或自身免疫性疾病。最后，早期免疫系统的开发改变在儿童癌症中起作用。最近的想法是，新生儿免疫系统是“胎儿”和“成人”成分之间相互作用的总和，但是，这些“系统”如何相互作用，过渡或影响新生儿的总体免疫组织化学。我们已经研究了小鼠免疫系统在生命的1-3周之间，因为许多方面都对中期妊娠和新生儿的免疫系统进行了建模。在此时间范围内，我们观察到了惊人的变化。例如，在T细胞完全填充吊臂之前，独特的红细胞谱系（EL）细胞在生命的第6天扩展到峰值，是囊中的主要种群几天，然后在生命的第21天之前收缩至接近成人水平。 EL的下降与袖子T细胞中的升高是伴随的。新生儿EL和成年CD4 T细胞之间的共培养导致IL-6的EL产生增加，进而导致CD4 T细胞的γIFN降低并增加IL-4的产生。 These observations and existing evidence suggesting that both EL and T cells respond to the growth factor IL-7 lead us to the novel overall hypothesis that in vivo expansion and contraction of EL as well as expansion of T cells in the neonatal spleen is regulated by competition for IL-7 and that activation of EL in this context increase EL-produced IL-6 which in turn directly supports "Th-2" differentiation in vivo during this period of neonatal life. R21应用中提出的工作利用了独特的遗传操纵小鼠，这是IL-6在调节免疫反应中作用的专家的经验，以及在T细胞稳态以及母体和新生儿免疫史的研究中的实验室经验。预计该结果将为您的早产和人类婴儿诊断免疫功能障碍的方法开发，并指导研究在新生儿时期增强保护性和调节不当免疫力的方法。