A5071041128- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Immune Response and Inflammation
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- Genomics, phytochemicals, and oxidative stress
- Cancer Immunotherapy and Biomarkers
- Adenosine and Purinergic Signaling
- Atherosclerosis and Cardiovascular Diseases
- Ubiquitin and proteasome pathways
- Hippo pathway signaling and YAP/TAZ
- Diet, Metabolism, and Disease
- Epigenetics and DNA Methylation
- Immune responses and vaccinations
- Diabetes and associated disorders
- Nutrition, Genetics, and Disease
- Pancreatic function and diabetes
- Biochemical and Molecular Research
- Quinazolinone synthesis and applications
- Protein Kinase Regulation and GTPase Signaling
- Reproductive System and Pregnancy
St. Jude Children's Research Hospital
2017-2024
Cincinnati Children's Hospital Medical Center
2010-2020
University of Cincinnati
2013-2020
University of Cincinnati Medical Center
2010-2020
T cells are integral in mediating adaptive immunity to infection, autoimmunity, and cancer. Upon immune challenge, exit from a quiescent state, followed by clonal expansion effector differentiation. These processes shaped three established signals, namely antigen stimulation (Signal 1), costimulation 2), cytokines 3). Emerging findings reveal that nutrients, including glucose, amino acids, lipids, crucial regulators of cell responses interplay with Signals 1-3, highlighting nutrients as...
Abstract We have previously shown that regulatory T cells (Treg) accumulate dramatically in aged animals and negatively impact the ability to control persistent infection. However, mechanisms underlying age-dependent accrual of Treg remain unclear. In this study, we show accumulation with age is progressive likely not result increased thymic output, peripheral proliferation, or from enhanced conversion. Instead, found mice are more resistant apoptosis than young mice. Although had expression...
Aging results in profound immune dysfunction, resulting the decline of vaccine responsiveness previously attributed to irreversible defects system. In addition increased interleukin-6 (IL-6), we found aged mice exhibit systemic IL-10 that requires forkhead box P3-negative (FoxP3-), but not FoxP3+, CD4+T cells. Most IL-10-producing cells manifested a T follicular helper (Tfh) phenotype and required Tfh cytokines IL-6 IL-21 for their accrual, so refer them as Tfh10 was also maintain normal...
c-Myc coordinates context-dependent homeostasis and transitional activation with metabolic programming of regulatory T cells.
Regulatory T cells (Tregs), a subset of CD4(+) cells, dramatically accumulate with age in humans and mice contribute to age-related immune suppression. Recently, we showed that majority accumulating Tregs aged expressed low levels CD25, their accrual is associated declining IL-2 mice. In this study, further investigated the origin CD25(lo) First, had high expression neuropilin-1 Helios, broad Vβ repertoire. Next, analyzed gene profile Tregs, naive memory We found were more related young than...
We and others have shown that regulatory T cells (Treg) accumulate dramatically with age in both humans mice. Such Treg accrual contributes to age-related immunosenescence as they reduce the response tumors parasite infection. While we reported earlier aged decreased expression of pro-apoptotic molecule Bim germline deletion promoted accumulation Treg, it remains unclear whether effects are: (i) intrinsic (ii) dominant other BH3-only molecules. Further, mechanism(s) controlling remain...
Cytomegalovirus (CMV) causes a persistent, lifelong infection. CMV persists in latent state and undergoes intermittent subclinical viral reactivation that is quelled by ongoing T cell responses. While cells are critical to maintain control of infection, the immunological factors promote persistence remain unclear. Here, we investigated role regulatory (Treg) mouse model infection using Foxp3-diphtheria toxin receptor (Foxp3-DTR) mice. Eight months after MCMV had established latency spleen,...
Invariant natural killer T (iNKT) cells acquire effector functions during development by mechanisms that remain poorly understood. Here, we show the Hippo kinases Mst1 and Mst2 act as molecular rheostats for terminal maturation differentiation programs of iNKT cells. Loss alone or together with impedes cell development, associated defective IL-15–dependent survival. Mechanistically, enforces cellular transcriptional quiescence commitment to iNKT1 suppressing proliferation Opa1-related...
Abstract Regulatory T (Treg) cell activation and expansion during neonatal life in response to inflammation are critical for immunosuppression, yet the mechanisms governing these events incompletely understood. We report that oncogene transcriptional regulator c-Myc (Myc) controls immune homeostasis through regulation of Treg accumulation functional activation. Myc activity is enriched cells generated responding inflammation. Myc-deficient show cell-intrinsic defects overall ability...
Abstract Type 1 regulatory T cells (Tr1) are a unique population of CD4+ Foxp3− that express high levels IL-10, and have been defined based on their expression CD49b LAG-3. Despite the critical roles played by Tr1 in controlling cell responses autoimmunity infection, mechanisms underlying homeostasis remain unclear. Here, we investigated homeostasis, phenotype function with age. We found accumulated dramatically Further, produced more IL-10 per compared to Foxp3+ Treg. While aged expressed...
Increasing evidence points to a key role for NK cells in controlling adaptive immune responses. In studies examining the of CD1d on CD4+ T cell responses, we found that line CD1d-deficient mice C57BL/6J background had homozygous 129 locus chromosome 6 containing entire gene cluster. Mice possessing this (C57BL/6.NKC129) displayed >10-fold reduction antigen-specific responses after intracranial infection with lymphocytic choriomeningitis virus (LCMV). Neither parental strain defects...