A5044747238- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Allergic Rhinitis and Sensitization
- Pediatric health and respiratory diseases
- Magnetism in coordination complexes
- Inhalation and Respiratory Drug Delivery
- Organic and Molecular Conductors Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- HIV Research and Treatment
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Immune Response and Inflammation
- Chemokine receptors and signaling
- Reproductive System and Pregnancy
- Air Quality and Health Impacts
- Transplantation: Methods and Outcomes
- Cytomegalovirus and herpesvirus research
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Sphingolipid Metabolism and Signaling
- Coordination Chemistry and Organometallics
National Institute of Environmental Health Sciences
2013-2022
National Institutes of Health
2013-2022
Triangle
2015-2022
Immunité et Cancer
2017
University of Chicago
2010-2012
Howard Hughes Medical Institute
2010-2012
Pulmonary and Critical Care Associates
2011
Massachusetts General Hospital
2003-2009
Harvard University
2004-2009
Center for Orthopaedics
2008
Cerebral malaria is a significant cause of global mortality, causing an estimated two million deaths per year, mainly in children. The pathogenesis this disease remains incompletely understood. Chemokines have been implicated the development cerebral malaria, and IFN-inducible CXCR3 chemokine ligand IP-10 (CXCL10) was recently found to be only serum biomarker that predicted mortality Ghanaian We show ligands Mig (CXCL9) were highly induced brains mice with murine caused by Plasmodium berghei...
Abstract CD1d-restricted T cells (NKT cells) are innate memory activated by lipid Ags and play important roles in the initiation regulation of immune response. However, little is known about trafficking patterns these or tissue compartment which they exert their regulatory activity. In this study, we determined chemokine receptor profile expressed found peripheral blood healthy volunteers as well cell clones. were identified Abs recognizing invariant Vα24 TCR rearrangement binding to CD1d-Fc...
Innate-like NKT cells conspicuously accumulate within the liver microvasculature of healthy mice, crawling on luminal side endothelial cells, but their general recirculation pattern and mechanism intravascular behavior have not been elucidated. Using parabiotic we demonstrated that, despite location, most failed to recirculate. Antibody blocking experiments established that they were retained locally through constitutive LFA-1–intercellular adhesion molecule (ICAM) 1 interactions. This...
The host response to intracellular pathogens requires the coordinated action of both innate and acquired immune systems. Chemokines play a critical role in trafficking cells transitioning an into response. We analyzed mice deficient chemokine receptor CCR5 following infection with protozoan parasite Toxoplasma gondii. found that controls recruitment natural killer (NK) infected tissues. Without this influx NK cells, tissues from CCR5-deficient (CCR5−/−) were less able generate inflammatory...
Endometriosis is a gynecological disease that negatively affects the health of 1 in 10 women. Although more information known about late stage disease, early initiation endometriosis and lesion development poorly understood. Herein, we use uterine tissue transfer mouse model to examine its dependence on estradiol (E2) estrogen receptor (ER) α within 72 hours initiation. Using wild-type ERα knockout mice as hosts or donors, find substantial infiltration neutrophils macrophages into peritoneal...
Abstract STAT6-mediated chemokine production in the lung is required for Th2 lymphocyte and eosinophil homing into airways allergic pulmonary inflammation, thus a potential therapeutic target asthma. However, critical cellular source of has not been defined. In this study, we demonstrate that STAT6 bone marrow-derived myeloid cells was sufficient CCL17, CCL22, CCL11, CCL24 recruitment airway. contrast, airway-lining did mediate or support recruitment. Selective depletion CD11b+ identified...
Airborne exposure to microbial cell wall lipids such as lipopolysaccharide triggers innate immune responses that regulate susceptibility allergic airway inflammation. α-Glycosylceramides represent another widespread class of directly stimulate innate-like, IL-4– and IL-13–producing, CD1d-restricted NKT cells. In this study, we demonstrate cells constitutively accumulate reside in the microvasculature mouse lung. After a single airborne lipid antigen, they promptly extravasate orchestrate...
Human allergic asthma is a chronic inflammatory disease of the airways thought to be driven by allergen-specific Th2 cells, which are recruited into lung in response inhaled allergen. To identify chemoattractant receptors that control this homing pattern, we used endobronchial segmental allergen challenge human atopic asthmatics define pattern receptor expression on T cells as well numbers CD1d-restricted NKT and levels chemokines bronchoalveolar (BAL) fluid. comprised only small minority...
α-Galactosylceramide represents a new class of vaccine adjuvants and immunomodulators that stimulate NKT cells to secrete Th1 Th2 cytokines. Synthetic variants with short or unsaturated acyl chains exhibit striking bias in vivo but no evidence defect TCR signaling stimulation vitro. Using cd1d1(fl/fl) mice, we demonstrated distinct APC types explained the cytokine vivo. Whereas by required CD1d expression dendritic (DCs), presentation was promiscuous unaffected DC-specific ablation CD1d....
Alveolar macrophages (AM) play a central role in initiation and resolution of lung inflammation, but the integration these opposing core functions is poorly understood. AM expression cholesterol 25-hydroxylase (CH25H), primary biosynthetic enzyme for 25-hydroxycholesterol (25HC), far exceeds other tissues, no CH25H has been defined biology. As 25HC an agonist antiinflammatory nuclear receptor, liver X receptor (LXR), we speculated that might regulate inflammatory homeostasis lung. Here, show...
Abstract The HIV-1 accessory proteins Vpr, Vpu, and Vif are essential for viral replication, their cytoplasmic production suggests that they should be processed recognition by CTLs. However, the extent to which these targeted in natural infection, as well precise CTL epitopes within them, remains defined. In this study, responses against were analyzed 60 HIV-1-infected individuals 10 HIV-1-negative controls using overlapping peptides spanning entire proteins. Peptide-specific IFN-γ was...
Leukotriene B4 is a lipid mediator that recently has been shown to have potent chemotactic activity for effector T lymphocytes mediated through its receptor, BLT1. Here, we developed novel murine model of acute lung rejection demonstrate BLT1 controls CD8+ cell trafficking into the and disruption signaling in cells reduces inflammation mortality model. In addition, used BLT1-deficient mice antagonist two tracheal transplant models transplantation importance recruitment allografts. We also...
Abstract Th1 and Th2 effector CD4+ T cells orchestrate distinct counterregulatory biological responses. To deliver effective tissue Th1- Th2-type responses, cell recruitment into must be differentially regulated. We show that tissue-derived STAT1 controls the trafficking of adoptively transferred, Ag-specific, wild-type lung. Trafficking is regulated as STAT6, which regulates trafficking, had no effect on deficiency did not alter trafficking. demonstrate control mediated through T-bet....
Inhalation of allergens and pathogens elicits multiple changes in a variety immune cell types the lung. Flow cytometry is powerful technique for quantitative analysis surface proteins on cells, but it provides no information localization migration patterns these cells within Similarly, chemotaxis assays can be performed to study potential respond chemotactic factors vitro, do not reproduce complex environment intact In contrast aforementioned techniques, location individual lung readily...
Asthma is associated with exposure to a wide variety of allergens and adjuvants. The extent which overlap exists between the cellular molecular mechanisms triggered by these various agents poorly understood, but it might explain differential responsiveness patients specific therapies. In particular, unclear why some, not all, benefit from blockade TNF. Here, we characterized signaling pathways distinct types adjuvants during allergic sensitization. Mice sensitized an innocuous protein using...
Humans with asthma display considerable heterogeneity regard to T helper (Th) 2-associated eosinophilic and Th17-associated neutrophilic inflammation, but the impact of environment on these different forms is poorly understood.We studied nature longevity asthma-like responses triggered by inhalation allergen together environmentally relevant doses inhaled lipopolysaccharide (LPS).Ovalbumin (OVA) was instilled into airways mice a wide range LPS doses. Following single OVA challenge, or...
Salts of the donor molecule, bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF or ET), with pentafluorothiomethylsulfonate (SF5CX2SO3-, X = H F) anions have been prepared. Three phases, β' '-(ET)2SF5CH2SO3, β'-(ET)2SF5CF2SO3, and '-(ET)2SF5CHFSO3 were obtained by electrocrystallization corresponding LiSF5CX2SO3 electrolytes. The structures these salts determined single-crystal X-ray diffraction, their physical properties examined electrical resistivity measurements as well ESR Raman...
Background: Arsenic exposure via drinking water impacts millions of people worldwide. Although arsenic has been associated epidemiologically with increased lung infections, the identity cell types targeted by peroral and immune mechanisms remain poorly defined. Objectives: We aimed to determine impact on pulmonary antibacterial host defense. Methods: Female C57BL/6 mice were administered 0, 250 ppb, or 25 ppm sodium arsenite for 5 wk then challenged intratracheally Klebsiella pneumoniae,...