A5067207426- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Diabetes and associated disorders
- Asthma and respiratory diseases
- Pancreatic function and diabetes
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
- Metabolism, Diabetes, and Cancer
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Psoriasis: Treatment and Pathogenesis
- Glycosylation and Glycoproteins Research
- Glaucoma and retinal disorders
- Galectins and Cancer Biology
- Indoor Air Quality and Microbial Exposure
- Neuroscience and Neuropharmacology Research
- Retinal Diseases and Treatments
- Corneal surgery and disorders
- Connective tissue disorders research
- Genetics and Neurodevelopmental Disorders
- Immunodeficiency and Autoimmune Disorders
- Air Quality and Health Impacts
- Dermatology and Skin Diseases
- Chemokine receptors and signaling
- Ocular Surface and Contact Lens
University of Colorado Denver
2011-2022
National Jewish Health
2009-2022
University of Colorado Anschutz Medical Campus
2015-2022
Howard Hughes Medical Institute
2011-2015
New York State Office for People With Developmental Disabilities
2013
Nantong University
2011
University of Colorado Health
2007-2009
Denver Health Medical Center
2007-2009
Uppsala University
2000
In the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D), an insulin peptide (B:9–23) is a major target for pathogenic CD4 + T cells. However, there no consensus on relative importance various positions or “registers” this can take when bound in groove NOD MHCII molecule, IA g7 . This has hindered structural studies and tracking relevant cells vivo with fluorescent peptide-MHCII tetramers. Using mutated B:9–23 peptides methods trapping particular registers, we show that most, if...
Allergic airway inflammation and hyperreactivity are modulated by gammadelta T cells, but different experimental parameters can influence the effects observed. For example, in sensitized C57BL/6 BALB/c mice, transient depletion of all TCR-delta(+) cells just before challenge resulted hyperresponsiveness (AHR), caused hyporesponsiveness when initiated i.p. sensitization. Vgamma4(+) strongly suppressed AHR; their relieved suppression challenge, not sensitization, they AHR transferred into...
Abnormal alternative splicing of tau exon 10 results in imbalance 3R-tau and 4R-tau expression, which is sufficient to cause neurofibrillary degeneration. Splicing factor SC35, a member the superfamily serine/arginine-rich (SR) proteins, promotes inclusion. The molecular mechanism by SC35 participates remains elusive. In present study, we found that pre-mRNA was coprecipitated tagged with HA. Mutation SC35-like exonic enhancer located at affected both binding promotion inclusion, suggesting...
Pulmonary gammadelta T cells protect the lung and its functions, but little is known about their distribution in this organ relationship to other pulmonary cells. We now show that alphabeta are distributed differently normal mouse lung. The have a bias for nonalveolar locations, with exception of airway mucosa. Subsets exhibit further variation tissue localization. frequently contact leukocytes, they favor different cell-types. an intrinsic preference F4/80+ major histocompatibility complex...
Impaired brain glucose uptake and metabolism precede the appearance of clinical symptoms in Alzheimer disease (AD). Neuronal transporter 3 (GLUT3) is decreased AD correlates with tau pathology. However, what leads to GLUT3 yet unknown. In this study, we found that promoter human contains three potential cAMP response element (CRE)-like elements, CRE1, CRE2 CRE3. Overexpression CRE-binding protein (CREB) or activation cAMP-dependent kinase significantly increased expression. CREB bound CREs...
Significance Type 1 diabetes is an autoimmune disease in which the insulin-producing beta cells within islets of Langerhans pancreas are destroyed by T cell-mediated immune attack. The peptide epitopes derived from islet proteins that targeted CD4 + have been difficult to determine. We show nonobese diabetic (NOD) mouse model a (WE14) chromogranin A likely posttranslationally modified create target epitope. hypothesize modification caused transpeptidation other peptides fused N terminus...
The identification of the peptide epitopes presented by major histocompatibility complex class II (MHCII) molecules that drive CD4 T cell component autoimmune diseases has a formidable challenge over several decades. In type 1 diabetes (T1D), recent insight into this problem come from realization important are not directly processed protein source, but rather pieced together fusion different fragments secretory granule proteins to create new chimeric epitopes. We have proposed is performed...
In type 1 diabetes, mouse and human CD4 + T cells recognize mutated chimeric superagonist insulin B-chain epitopes similarly.
Abstract The Vγ4+ pulmonary subset of γδ T cells regulates innate airway responsiveness in the absence αβ cells. We now have examined same a model allergic disease, OVA-sensitized and challenged mice that exhibit Th2 responses, inflammation, hyperreactivity (AHR). In sensitized mice, preferentially increased number following challenge. Depletion before challenge substantially AHR these but had no effect on normal, nonchallenged mice. Vγ1+ AHR, depletion all TCR-δ+ was more effective than...
Abstract It has been reported that the IgE response to allergens is influenced by γδ T cells. Intrigued a study showing airway challenge of mice with OVA induces in spleen development cells suppress primary i.p.-injected OVA-alum, we investigated involved. We found induced suppressors are contained within Vγ4+ subset spleen, they express Vδ5 and CD8, depend on IFN-γ for their function. However, also normal nonchallenged harbor IgE-enhancing cells, which larger Vγ1+ spleen. In cell transfer...
Abstract Mice sensitized and challenged with OVA were used to investigate the role of innate T cells in development allergic airway hyperresponsiveness (AHR). AHR, but not eosinophilic inflammation, was induced cell-deficient mice by small numbers cotransferred γδ invariant NKT cells, whereas either cell type alone effective. Only Vγ1+Vδ5+ enhanced AHR. Surprisingly, OVA-specific αβ required, revealing a pathway AHR mediated entirely cells. The data suggest that lymphocytic synergism, which...
Abstract Airway hyperresponsiveness (AHR), a hallmark of asthma and several other diseases, can be modulated by γδ T cells. In mice sensitized challenged with OVA, AHR depends on allergen-specific αβ cells; but Vγ1+ cells spontaneously enhance AHR, whereas Vγ4+ cells, after being induced airway challenge, suppress AHR. The activity these cell modulators is allergen nonspecific, how they develop unclear. We now show that CD8 essential for the development both suppressor enhancer although...
Abstract γδ T cells suppress airway hyperresponsiveness (AHR) induced in allergen-challenged mice but it is not clear whether the suppression allergen specific. The AHR-suppressive express TCR-Vγ4. To test suppressive function must be induced, we adoptively transferred purified Vγ4+ into cell-deficient and OVA-sensitized -challenged recipients (B6.TCR-Vγ4−/−/6−/−) measured effect on AHR. isolated from naive donors were AHR-suppressive, OVA-stimulated suppressed Suppressive could lung spleen....
gammadelta T cells regulate airway reactivity, but their role in ozone (O3)-induced hyperresponsiveness (AHR) is not known. Our objective was to determine the of O3-induced AHR. Different strains mice, including those that were genetically manipulated or antibody-depleted render them deficient total specific subsets cells, exposed 2.0 ppm O3 for 3 hours. Airway reactivity inhaled methacholine, inflammation, and epithelial cell damage monitored. Exposure C57BL/6 mice resulted a transient...
Allergic airway hyperresponsiveness (AHR) in OVA-sensitized and challenged mice, mediated by allergen-specific Th2 cells Th2-like invariant NKT (iNKT) cells, develops under the influence of enhancing inhibitory gammadelta T cells. The AHR-enhancing belong to Vgamma1(+) cell subset, that are capable increasing IL-5 IL-13 levels airways a manner like They also synergize with iNKT mediating AHR. However, unlike AHR enhancers arise untreated we show here they exhibit their functional bias...
Influenza virus poses a difficult challenge for protective immunity. This is adept at altering its surface proteins, the proteins that are targets of neutralizing antibody. Consequently, each year new vaccine must be developed to combat current recirculating strains. A universal influenza primes specific memory cells recognise conserved parts could prove effective against both annual variants and newly emergent potentially pandemic Such will have contain safe adjuvant can used in individuals...
B cell hybridomas are an important source of monoclonal antibodies. In this paper, we developed a high-throughput method to characterize mouse IgG antibodies using surface plasmon resonance technology. This assay rapidly determines their sub-isotypes, whether they bind native antigen and approximate affinities for the only 50 μl hybridoma culture supernatant. Moreover, found that secreting also have membrane form expression without Igα. Based on IgG, used flow cytometry isolate rare γ2a...