A5002342267- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Lymphoma Diagnosis and Treatment
- Food Allergy and Anaphylaxis Research
- Eosinophilic Esophagitis
- Influenza Virus Research Studies
- Immunodeficiency and Autoimmune Disorders
- Eosinophilic Disorders and Syndromes
- Asthma and respiratory diseases
- Connective tissue disorders research
- IL-33, ST2, and ILC Pathways
- Viral gastroenteritis research and epidemiology
- Mast cells and histamine
- Aortic Disease and Treatment Approaches
- Transgenic Plants and Applications
- Biosimilars and Bioanalytical Methods
- Aortic aneurysm repair treatments
- Immune responses and vaccinations
National Institutes of Health
2017-2024
National Cancer Institute
2022-2024
National Institute of Allergy and Infectious Diseases
2017-2024
Center for Cancer Research
2024
The Wistar Institute
2012-2015
University of Pennsylvania
2012
The aortic root is the predominant site for development of aneurysm caused by heterozygous loss-of-function mutations in positive effectors transforming growth factor-β (TGF-β) pathway. Using a mouse model Loeys-Dietz syndrome (LDS) that carries kinase-inactivating mutation TGF-β receptor I, we found effects this depend on lineage origin vascular smooth muscle cells (VSMCs). Secondary heart field–derived (SHF-derived), but not neighboring cardiac neural crest–derived (CNC-derived), VSMCs...
Allergic diseases are a global health challenge. Individuals harboring loss-of-function variants in transforming growth factor–β receptor (TGFβR) genes have an increased prevalence of allergic disorders, including eosinophilic esophagitis. typically localize to mucosal barriers, implicating epithelial dysfunction as cardinal feature disease. Here, we describe essential role for TGFβ the control tissue-specific immune homeostasis that provides mechanistic insight into these clinical...
Allergic diseases are common, affecting more than 20% of the population. Genetic variants in TGFβ pathway strongly associated with atopy. To interrogate mechanisms underlying this association, we examined patients and mice Loeys-Dietz syndrome (LDS) who harbor missense mutations kinase domain TGFΒR1/2 . We demonstrate that LDS lead to reduced signaling elevated total allergen-specific IgE, despite presence wild-type T regulatory cells a chimera model. Germinal center activity was enhanced...
We examined the formation, participation, and functional specialization of virus-reactive Foxp3(+) regulatory T cells (Tregs) in a mouse model influenza virus infection. "Natural" Tregs generated intrathymically, based on interactions with self-peptide, proliferated response to homologous viral Ag lungs and, lesser extent, lung-draining mediastinal lymph nodes (medLNs) virus-infected mice. In contrast, conventional CD4(+) identical TCR specificity underwent little or no conversion become...
Autoreactive CD4(+) CD8(-) (CD4SP) thymocytes can be subjected to deletion when they encounter self-peptide during their development, but also undergo selection become CD4SPFoxp3(+) Treg cells. We have analyzed the relationship between these distinct developmental fates using mice in which signals transmitted by TCR been attenuated mutation of a critical tyrosine residue adapter protein SLP-76. In containing polyclonal repertoires, caused increased frequencies thymocytes. CD4SP expressing...
T cells expressing anti-CD19 chimeric antigen receptors (CARs) have activity against chronic lymphocytic leukemia (CLL), but complete response rates range from 18% to 29%, so improvement is needed. Peripheral blood mononuclear (PBMCs) of CLL patients often contain high levels that can interfere with CAR cell production, and are prone exhaustion other functional defects. We previously developed an designated Hu19-CD828Z. Hu19-CD828Z has a binding domain derived fully human antibody CD28...
This article introduces a series of reviews covering Regulatory Cells in Health and Disease appearing Volume 259 Immunological Reviews. The adaptive immune system endows vertebrates with the ability to identify target pathogens for elimination during primary infections form memory cells that provide accelerated responses and/or protection upon subsequent encounters pathogen. One pillars modern immunology is clonal selection theory first put forward by Burnet 1, which posits there exists body...
Abstract How the formation and activity of CD4+Foxp3+ regulatory T cells (Tregs) are shaped by TCR recognition diverse array peptide:MHC complexes that can be generated from self-antigens and/or foreign Ags in vivo remains poorly understood. We show a self-peptide with low (but not high) stimulatory potency promotes thymic Treg induce conventional CD4+ periphery to become Tregs express different levels transcription factor Helios according anatomical location. When response this subsequently...
Abstract Loeys-Dietz syndrome (LDS) is an autosomal dominant disorder caused by mutations in genes encoding proteins the transforming growth factor beta (TGFβ) signaling pathway. Patients heterozygous for a point mutation kinase domain of TGFβR1 (TGFBR1M318R) exhibit classic manifestations LDS. Mice with this were made hope that animal model LDS will lead to better understanding mechanisms underlying symptoms. TGFBR1M318R+/− mice hallmark skeletal and cardiovascular phenotypes We sought...
Abstract We have examined the formation, participation and functional specialization of virus-reactive Foxp3+ regulatory T cells (Tregs) in a mouse model influenza virus infection. “Natural” Tregs generated intra-thymically based on interactions with self-peptide proliferated response to homologous viral antigen lungs, lesser extent lung-draining mediastinal LN (medLN), virus-infected mice. By contrast, conventional CD4+ identical TCR specificity underwent little or no conversion become...
Abstract It is generally accepted that developing thymocytes can become Foxp3+ regulatory T cells (Tregs) through recognition of self-antigens during thymic selection. Tregs also develop from conventional CD4+ responding to exogenously administered peptides (including food antigens) in vivo, and via TGF-β signaling activation vitro, but the processes by which Treg induction may occur response self-peptides periphery remain unclear. We are examining this question transferring CD4+CD25-Foxp3-...
Peanut allergy is potentially life-threatening and generally has a poor prognosis. Recent data suggests the skin may be an important route of initial sensitization to peanut, that early oral exposure peanut protective. In mice, Tregs are central development tolerance food, although definitive in humans lacking. We sought quantify phenotype peanut-specific Teffs individuals with without allergy. Whole blood was obtained from allergic non-sensitized/non-allergic stimulated crude extract or...
Abstract Transforming growth factor-β receptor (TGF-βR) signaling is important in regulating the proliferation and differentiation of CD4+ T cells, but how modulating level can affect cell fate remains unclear. We have created a mouse model Loeys-Dietz syndrome (LDS), an autosomal dominant disease caused by mutations genes encoding TGF-βR, targeting missense mutation (M318R) to endogenous murine Tgfbr1 locus. LDS patients exhibit increased propensity for allergic disease, no overt...
Abstract T follicular helper (Tfh) cells are a subset of CD4+ that play crucial role in the development memory B and plasma cells. regulatory (Tfr) oppose Tfh suppress humoral immune responses. Patients with Loeys-Dietz Syndrome (LDS) type 1 2 have an autosomal dominant mutation genes encoding TGFβ Receptor or 2, respectively, strong predisposition to develop allergic diseases. We hypothesized altered function could contribute increased IgE-mediated phenotypes LDS. Comparing cohort pediatric...