Document text
Principal Investigator: Derek B. Sant'Angelo
Organization: RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
Fiscal Year: 2020
Award: $477,000
Funding agency: National Institute of Allergy and Infectious Diseases
Summary
There are at least 49 members of the BTB-ZF gene family, which includes PLZF, BCL6, ThPOK, LRF and
others. Only a few have been studied in the context of immune system development or function. Expression of
the known BTB-ZF genes correlates with specific functions of the cells – in many ways, the BTB-ZF gene
actually defines the subset. Therefore, our lab has hypothesized that analysis of BTB-ZF gene expression at
the level of the single cell will result in the identification of new T cell subsets. What is clear is that
understanding the diversity of lymphocyte subsets defined by this gene family will have a profound impact on
our understanding of the overall complexity and function of the immune response. Indeed, the identification of
novel immune subsets, such as Th17 T cells, Tregs, Tfh cells, has proven over the last few years to have
major implications for vaccine development, cancer treatment and the management of autoimmune diseases.
In this application, we show that that a specific BTB-ZF family member defines a unique subset of CD4+ T cells
and a subset of Tregs. Through the use of genetically engineered mouse models we show that these cells
rapidly produce effector cytokines following stimulation. We also show that, analogous to NKT cells, these cells
have “pre-formed” cytokine message. The significance of this application lies in the definition of two novel T
cell subsets that we hypothesize play unique roles in immune homeostasis. In this application, using
genetically modified mice, adoptive cell transfers and disease models, we will study the functions of these cells
particularly when they are resident in specific tissues. We also will explore the interrelationships between the
cells in spleen, intestine and visceral fat.
Terms: <Adipocytes><Adipose Cell><Adipose tissue><Adoptive Cell Transfers><Adult-Onset Diabetes Mellitus><Antigens><Autoimmune Diseases><Autoregulation><B cell lymphoma 6><B-Cell CLL/Lymphoma-6 Gene><BCL5><BCL6><BCL6 gene><Basal Transcription Factor><Basal transcription factor genes><Body Tissues><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CSIF><CSIF-10><Cancer Treatment><Cell Body><Cell Function><Cell Process><Cell physiology><Cells><Cellular Function><Cellular Immune Function><Cellular Physiology><Cellular Process><Cys-His2 Zinc Finger Transcription Factor Gene><Cytokine Synthesis Inhibitory Factor><Data><Disease model><Family member><Fat Cells><Fats><Fatty Tissue><Fatty acid glycerol esters><Frequencies><GEM model><Gene Expression><Gene Family><General Transcription Factor Gene><General Transcription Factors><Genes><Genetically Engineered Mouse><Homeostasis><IL-10><IL10><IL10A><Immune><Immune response><Immune system><Immunes><Immunological response><Immunomodulation><Inflammation><Interleukin 10 Precursor><Interleukin-10><Intestinal><Intestines><Ketosis-Resistant Diabetes Mellitus><LAZ-3 Gene><LAZ3><Lamina Propria><Leanness><Lipocytes><Lymphocyte><Lymphocyte Subpopulations><Lymphocyte Subset><Lymphocytic><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Mature Lipocyte><Mature fat cell><Maturity-Onset Diabetes Mellitus><Messenger RNA><Mice><Mice Mammals><Molecular><Murine><Mus><NIDDM><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Obese Mice><Obesity><PLZF><PPAR gamma><PPAR-γ><PPARgamma><PPARγ><Peroxisome Proliferative Activated Receptor Gamma><Peroxisome Proliferator-Activated Receptor gamma><Peroxisome Proliferator-Activated Receptor γ><Phenotype><Physiological Homeostasis><Play><Population><Process><Promyelocytic Leukemia Zinc Finger><RNA Seq><RNA sequencing><RNAseq><Regulatory T-Lymphocyte><Risk Factors><Role><Site><Slow-Onset Diabetes Mellitus><Spleen><Spleen Reticuloendothelial System><Stable Diabetes Mellitus><Subcellular Process><Systems Development><T-Cell Subsets><T-Cells><T-Lymphocyte><T-Lymphocyte Subsets><T2 DM><T2D><T2DM><T4 Cells><T4 Lymphocytes><Thiazolidinedione Receptor><Thinness><Thymic Tissue><Thymus><Thymus Gland><Thymus Proper><Thymus Reticuloendothelial System><Tissues><Transcription Factor Proto-Oncogene><Transcription factor genes><Treg><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><Visceral><Visceral fat><ZBTB16><ZNF145><ZNF145 gene><ZNF51><ZNF51 Gene><Zinc Finger Protein 145><Zinc Finger Protein 51 Gene><Zinc Finger- and BTB Domain-Containing Protein 16><adipose><adiposity><adoptive cell therapy><adoptive cellular therapy><adult onset diabetes><allergic/immunologic body system><allergic/immunologic organ system><anti-cancer therapy><anticancer therapy><autoimmune disorder><bowel><cancer therapy><corpulence><corpulency><corpulentia><cytokine><develop a vaccine><development of a vaccine><differential expression><differentially expressed><disorder model><effector T cell><genetically engineered mouse model><genetically engineered murine model><global gene expression><global transcription profile><host response><immune function><immune modulation><immune regulation><immune regulator><immunogen><immunologic reactivity control><immunomodulatory><immunoregulation><immunoregulatory><immunoresponse><innovate><innovation><innovative><insight><intraepithelial><ketosis resistant diabetes><lymph cell><mRNA><maturity onset diabetes><member><novel><ob/ob mouse><obese><obese people><obese person><obese population><prevent><preventing><regulatory T-cells><social role><thymus derived lymphocyte><transcription factor><transcriptional differences><transcriptome><transcriptome sequencing><type 2 DM><type II DM><type two diabetes><vaccine development><vaccine formulation><white adipose tissue><yellow adipose tissue>