A5004766529- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- Reproductive System and Pregnancy
- Kawasaki Disease and Coronary Complications
- Ocular Diseases and Behçet’s Syndrome
- Diabetes and associated disorders
- Adenosine and Purinergic Signaling
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Autoimmune and Inflammatory Disorders Research
- Cardiac Structural Anomalies and Repair
- IgG4-Related and Inflammatory Diseases
- Vasculitis and related conditions
- CAR-T cell therapy research
- SARS-CoV-2 and COVID-19 Research
- Electrolyte and hormonal disorders
- Renal function and acid-base balance
- Genetics and Neurodevelopmental Disorders
- Blood disorders and treatments
- Psoriasis: Treatment and Pathogenesis
- Whipple's Disease and Interleukins
- Pneumocystis jirovecii pneumonia detection and treatment
- Craniofacial Disorders and Treatments
St. Louis Children's Hospital
2025
Washington University in St. Louis
2020-2024
Center for Rheumatology
2021-2022
Medical College of Wisconsin
2011-2016
Johannes Gutenberg University Mainz
2015
University of Pittsburgh Medical Center
2011
University of Pittsburgh
2010
CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells are essential to the balance between pro- and anti-inflammatory responses. There two major subsets of Treg cells, "natural" (nTreg) that develop in thymus, "induced" (iTreg) arise periphery from Foxp3(-) conventional can be generated vitro. Previous work has established both required for immunological tolerance. Additionally, vitro-derived iTreg reestablish tolerance situations where decreased or defective. This review will focus on drawing...
Abstract “Natural” regulatory T cells (nTregs) that express the transcription factor Foxp3 and produce IL-10 are required for systemic immunological tolerance. “Induced” (iTregs) nonredundant essential tolerance at mucosal surfaces, yet their mechanisms of suppression stability unknown. We investigated role iTreg-produced iTreg fate in a treatment model inflammatory bowel disease. Colitis was induced Rag1−/− mice by adoptive transfer naive CD4+ carrying nonfunctional allele. At onset weight...
Germline gain-of-function (GOF) variants in STAT3 cause an inborn error of immunity associated with early-onset poly-autoimmunity and immune dysregulation. To study tissue-specific dysregulation, we used a mouse model carrying missense variant (p.G421R) that causes human disease. We observed spontaneous imiquimod (IMQ)-induced skin inflammation cell-intrinsic local Th17 responses GOF mice. CD4+ T cells were sufficient to drive showed increased Il22 expression expanded clones. Certain aspects...
Genetic testing has increased the number of variants identified in disease genes, but diagnostic utility is limited by lack understanding variant function. CARD11 encodes an adaptor protein that expresses dominant-negative and gain-of-function associated with distinct immunodeficiencies. Here, we used a "cloning-free" saturation genome editing approach diploid cell line to simultaneously score 2,542 for decreased or function region immunodeficiency. We also described exon-skipping mechanism...
Induced regulatory T (iTreg) and Th17 cells promote mucosal homeostasis. We used a cell transfer model of colitis to compare the capacity iTreg develop in situ following naive CD4(+)CD45RB(hi)T intoRag1(-/-)C57BL/6 or BALB/c mice, prototypical Th1/M1- Th2/M2-prone strains. found that frequency number Foxp3(+)iTreg were significantly reduced C57BL/6 mice compared with strain. also resistant natural Treg immunotherapy. Pretreatment C57BL/6Rag1(-/-)mice IL-4 plus IL-13, M2a but not M1...
Primary immune regulatory disorders (PIRD) represent a group of characterized by dysregulation, presenting with wide range clinical disease, including autoimmunity, autoinflammation, or lymphoproliferation. Autosomal dominant germline gain-of-function (GOF) variants in STAT3 result PIRD broad spectrum. Studies patients have documented decreased frequency FOXP3+ Tregs and an increased Th17 cells some active disease. However, the mechanisms disease pathogenesis GOF syndrome remain largely...
Summary Background: The incidence, severity, and risk factors for the development of hyponatremia in patients undergoing craniosynostosis surgery are not well known. Objective: To determine incidence severity as a complication surgical correction to identify postoperative hyponatremia. Methods: A retrospective medical record review 2003–2008 Cleft Craniofacial Database was made. Specific data collected included sodium values, age, weight, type surgery, duration administration DDAVP,...
Primary immunodeficiency diseases (PIDs) are a rapidly growing, heterogeneous group of genetically determined characterized by defects in the immune system. While individually rare, collectively PIDs affect between 1/1,000 and 1/5,000 people worldwide. The clinical manifestations vary from susceptibility to infections autoimmunity bone marrow failure. Our understanding human response has advanced investigation discovery genetic mechanisms PIDs. Studying patients with isolated variants...
To study regulatory T (Treg) cell control of chronic autoimmunity in a lymphoreplete host, we created and characterized new model autoimmune lung inflammation that targets the medium small airways. We generated transgenic mice express chimeric membrane protein consisting hen egg lysozyme hemoglobin epitope tag under Clara secretory promoter, which largely limited transgene expression to respiratory bronchioles. When protein-membrane lysozyme/hemoglobin were crossed N3.L2 TCR recognize...
Abstract Regulation of T cell signaling is paramount to mount an appropriate immune response and protect the host from pathophysiology. Here, we study impact on CD8+ cells in monogenic inborn error immunity patients exhibiting dysregulated signal 3 (cytokine signaling) pathways resulting STAT3 gain- or loss-of-function variants (STAT3 GOF LOF). Using high dimensional profiling, demonstrate increased expression ectoenzyme, CD39, which hydrolyzes extracellular ATP, patient cells. Moreover, two...
Signal transduction downstream of activating stimuli controls CD8+ T cell biology, however these external inputs can become uncoupled from transcriptional regulation in Primary Immune Regulatory Disorders (PIRDs). Gain-of-function (GOF) variants STAT3 amplify cytokine signaling and cause a severe PIRD characterized by early onset autoimmunity, lymphoproliferation, recurrent infections, immune dysregulation. In both primary human mouse models GOF, cells have been implicated as pathogenic...
Constrictive pericarditis is the final common result of a number processes that affect pericardium. Establishing diagnosis and determining underlying etiology constrictive are often diagnostic rendezvous. Here, we describe patient who presented to general practitioner with edema, ascites, weight gain was found have secondary an inflammatory myofibroblastic tumor mediastinum. Interestingly, she had relative lack cardiorespiratory complaints, and, aside from edema mildly elevated jugular...
Der klinische Verlauf einer Hepatitis hängt entscheidend vom Charakter der zu Grunde liegenden CD4+ T-Zellantwort ab. Die Immunantwort T-Zellen wird dabei von den Antigen-präsentierenden Zellen Leber bestimmt. Hepatozyten erwerben bei die Fähigkeit, MHC II-Moleküle auf ihrer Oberfläche exprimieren und somit eine induzieren.
Naïve peripheral T cells can express the transcription factor Foxp3 and develop regulatory function. These “induced” (iTreg) are essential for tolerance complement function of other populations. In this study we used lymphopenia-associated model colitis to compare kinetics iTreg cell production in both C57BL/6 BALB/c mice, prototypical Th1- Th2-type strains. Following adoptive transfer naïve CD4+ into Rag−/− recipients, tracked development over a period 40 days. Whereas was minimal, by 10...
Induced Treg (iTreg) cells are essential for tolerance. Although in vitro derived iTreg can be used therapeutically preclinical models of autoimmune disease, their stability vivo and mechanisms suppression have not been examined. Here, we a treatment model lymphopenia-associated colitis to examine the role IL-10 cell function. Monotherapy with sufficient but deficient slowed onset decreased colon infiltration, did resolve disease. Mice treated both nTreg survived gained weight when was...
Abstract It is still unknown whether primary immune regulatory disorders (PIRD) due to genetic variants that amplify T cell receptor and/or inflammatory cytokine signaling yield exhaustion. Here, we investigate the impact of dysregulated on CD8 +T cells in STAT3 gain-of-function (STAT3 GOF) patients. Immune profiling via 43-parameter CyTOF reveals altered differentiation, including loss naïve cells, increased frequency effector memory and EMRAcells, downregulation markers stemness (i.e.,...