A5101708950- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Asthma and respiratory diseases
- Immunodeficiency and Autoimmune Disorders
- IL-33, ST2, and ILC Pathways
- Psoriasis: Treatment and Pathogenesis
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Cytomegalovirus and herpesvirus research
- Phagocytosis and Immune Regulation
- Hematopoietic Stem Cell Transplantation
- Acute Lymphoblastic Leukemia research
- NF-κB Signaling Pathways
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Atherosclerosis and Cardiovascular Diseases
- Tuberculosis Research and Epidemiology
- Diabetes and associated disorders
- Viral gastroenteritis research and epidemiology
- Neonatal Respiratory Health Research
- Cytokine Signaling Pathways and Interactions
University of Alabama at Birmingham
2015-2023
Indiana University School of Medicine
2010-2017
Indiana University – Purdue University Indianapolis
2010-2017
University of Indianapolis
2011-2015
Center for Children
2014
Riley Hospital for Children
2013
Oregon State University
2009-2012
Bipar
2011
Abstract Th cell effector subsets develop in response to specific cytokine environments. The development of a particular cytokine-secreting pattern requires an integration signals that may promote the opposing pathways. A recent example this paradigm is IL-9–secreting Th9 develops TGF-β and IL-4, cytokines that, isolation, inducible regulatory T cells Th2 cells, respectively. To determine how balance these factors results priming for IL-9 secretion, we examined effects each pathway on...
In response to infection, naïve CD4+ T cells differentiate into two subpopulations: follicular helper (TFH) cells, which support B cell antibody production, and non-TFH enhance innate immune functions. Interleukin-2 (IL-2), the major cytokine produced by plays an important role in developmental divergence of these populations. However, relationship between IL-2 production fate determination remains unclear. Using reporter mice, we found that differential defined precursors fated for...
The ligand-activated transcription factor, aryl hydrocarbon receptor (AHR), is a novel inducer of adaptive Tregs. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most potent AHR ligand, induces CD4+CD25+ Tregs during an acute graft-versus-host (GvH) response and prevents generation allospecific cytotoxic T lymphocytes. TCDD also suppresses induction experimental autoimmune encephalitis in association with expanded population Foxp3+ In this study, we show that chronic treatment NOD mice...
ABSTRACT Recent evidence has identified the role of granzyme B- and perforin-expressing CD4 + T cells with cytotoxic potential in antiviral immunity. However, vivo cytokine cues downstream pathways governing differentiation these are unclear. Here, we have that specifically induced at site infection during influenza virus infection. The development was dependent on cooperation STAT2-dependent type I interferon signaling interleukin-2/interleukin-2 receptor alpha pathway for induction...
Abstract Although the activator protein‐1 (AP‐1) factor Batf is required for Th17 cell development, its mechanisms of action to underpin program are incompletely understood. Here, we find that ensures identity in part by restricting alternative gene programs through actions restrain IL‐2 expression and IL‐2‐induced Stat5 activation. This, turn, limits Stat5‐dependent recruitment Ets1‐Runx1 factors Th1‐ Treg‐cell‐specific loci. Thus, addition pioneering regulatory elements Th17‐specific loci,...
A transcription factor network that includes STAT4, T-bet, and Runx3 promotes the differentiation of Th1 cells inflammatory immune responses. How additional factors regulate function has not been defined. In this study we show negative regulatory Twist1 decreases expression Runx3, IL-12Rβ2 as it inhibits IFN-γ production. Ectopic but T-bet or IL-12Rβ2, compensates for effects on production, regulation Ifng depends complex formation with Runx3. binding at locus, chromatin looping within...
The IL-9-secreting Th9 subset of CD4 Th cells develop in response to an environment containing IL-4 and TGF-β, promoting allergic disease, autoimmunity, resistance pathogens. We previously identified a requirement for the ETS family transcription factor PU.1 development. In this report, we demonstrate that variant 5 (ETV5) promotes IL-9 production by binding recruiting histone acetyltransferases Il9 locus at sites distinct from PU.1. are deficient both ETV5 there is lower than lacking either...
Cytokine responsiveness is a critical component of the ability cells to respond extracellular milieu. Transcription factor-mediated regulation cytokine receptor expression common mode altering responses external environment. We identify transcription factor Twist1 as STAT3-induced feedback loop that controls IL-6 signals by directly repressing Il6ra. Human and mouse T lacking have an increased differentiate into Th17 cells. Mice with cell-specific deletion demonstrate follicular helper cell...
Activation of the aryl hydrocarbon receptor (AhR) by its prototypic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mediates potent suppression T-cell dependent immune responses. The suppressive effects TCDD occur early during CD4(+) differentiation in absence on proliferation and have recently been associated with induction AhR-dependent regulatory T-cells (Treg). Since AhR functions as a ligand-activated transcription factor, changes gene expression induced stages are likely to reflect...
PU.1 is an ETS family transcription factor that important for the development of multiple hematopoietic cell lineages. Previous work demonstrated a critical role in promoting Th9 and limiting Th2 cytokine production. Whether has functions other Th lineages not clear. In this study, we examined effects ectopic expression CD4(+) T cells observed decreased genes involved with function follicular helper (Tfh) cells, including Il21 Tnfsf5 (encoding CD40L). from conditional mutant mice lack...
Abstract Th17 cells are critical for the clearance of extracellular bacteria and fungi, but also contribute to pathology autoimmune diseases allergic inflammation. After exposure an appropriate cytokine environment, can acquire a Th1-like phenotype, less is known about their ability adopt Th2 Th9 effector programs. To explore this in more detail, we used IL-17F lineage tracer mouse strain that allows tracking formerly expressed IL-17F. In vitro–derived adopted signature transcription factor...
Abstract IFN regulatory factor 4 (IRF4) is a key transcription that promotes effector CD8+ T cell differentiation and expansion. The roles of IRF4 in regulating the response to cytokines have not been explored. In this article, we show IL-2 IL-15 signaling STAT5 activation regulate expression cells. Gene-expression profile analysis has also revealed required for receptors family CD122 CD127. We found binds directly CD127 gene loci, indicating it may promote transcription. As consequence,...
Summary IL-22 is a key cytokine in immune defense against pathogens at barrier sites. In response to enteric attaching and effacing bacteria, produced by type 3 innate lymphoid cells (ILC3s) thought be important early for induction of antimicrobial peptides (AMPs) that protect intestinal epithelial (IECs) advance T cell-derived arises later. Yet, the basis requirement both adaptive IL-22–producing protecting mucosa unknown. Here, using novel mice report expression can targeted its...
Abstract Inflammatory bowel disease (IBD) is an immune-mediated of the intestinal tract caused by chronic inflammation that can be relapsing and remitting. This leads to flares often require patients treated with life-long biologic therapy. Interleukin 10 (IL-10) immunosuppressive cytokine produced effector T cells, especially regulatory cells (Tregs), limit inflammatory responses both foreign self-antigens. Although IL-10-producing peripheral Tregs (IL-10+ pTregs) are thought play a...
Abstract T helper type 17 (Th17) cells secrete IL-17A, IL-17F, IL-21, and IL-22 cytokines can provide protection against extracellular pathogens or promote certain immune-mediated diseases. The basic leucine zipper transcription factor ATF-like (Batf) contributes to the transcriptional programming of multiple effector but is indispensable for Th17 cell development. Here, we have interrogated mechanisms by which Batf may act stabilize phenotype. We find that in vitro differentiated increased...