Credit: Image created with BioRender at Brusko Lab
The early life events that influence immune system development have implications in the development of a multitude of diseases including type 1 diabetes (T1D). The immune system is actively evolving and integrating dynamic signals from the host’s environment, not only to ward off external infection but also to respond to and participate in tissue growth and remodeling. The critical processes that determine immune tolerance or autoimmunity are shaped by these exposures. While much has been learned regarding the developing immune system in animal models, many knowledge gaps exist with respect to early human immune system development, including the fundamental processes involved in establishing self-tolerance, and how early adaptive immune responses are generated to the many diverse antigens and pathogens encountered during infancy and childhood. Access to human tissues, innovative research technologies, and analytic and data sharing capabilities are unprecedented and can now be leveraged to gain new insights. The purpose of HANDEL-1 program is to better understand the “normal” human immune developmental program by acquiring stromal and mucosal tissues from infant and pediatric organ donors and to create a novel and essential dataset informing immune system development in a collaborative research project that leverages shared access to various tissues in conjunction with the existing HANDEL-P program that seeks to understand the development of the pancreas and islet microenvironment in early life.
Human Atlas of Neonatal Development and Early Life-Immunity (HANDEL-I)
Project Dates: 04/01/2018-03/31/2021
Aims: Our aims are to conduct transcriptional profiling of stromal and APC populations within immunologically active developmental tissues and to conduct flow cytometric profiling and bulk RNAseq analysis of FACS-isolated lymphocyte subsets. We are in progress of analyzing the changes in gene expression that accompany export of T cells from developmental sites to the periphery by applying single cell transcriptome profiling on T and B cells using the 10X Genomics Chromium Platform. Other goals under this grant include determining how the T cell and DC subset composition and localization in mucosal and lymphoid tissues is altered as a function of age during infancy and early childhood by tissue imaging using fluorescence microscopy focusing on the frequency and tissue location of naive, Treg, effector, meomory and tissue-resident memory T cells (TRM).
Data Processing and sharing: Data will also be deposited in a Google Genomics Cloud Platform (with associated APIs) for data integration and sharing with HANDEL-P investigators.
- UF Pathology News: Dr. Todd Brusko, Associate Professor in the Experimental Pathology Division and Diabetes Institute at the University of Florida, was awarded $1.78M from the Leona & Harry Helmsley Charitable Trust for a three year project on Type 1 Diabetes.
- Dr. Brusko heads a HELMSLEY CHARITABLE TRUST supported effort to profile the developing human immune system during early life, referred to as the Human Atlas of Neonatal Development and Early Life –Immunity (HANDEL-I).