David B Corry

Baylor College of Medicine, Houston, Texas, United States

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Publications (114)969.13 Total impact

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    ABSTRACT: The leukotrienes (LTs) enhance allergen- and interleukin (IL)-13-dependent allergic lung inflammatory disease. However, the precise requirement of LTs and the mechanism by which they elicit allergic lung responses remain uncertain. To clarify the involvement of LTs in respiratory allergen- and IL-13-induced experimental asthma and elucidate the underlying mechanisms of LTs-mediated enhanced allergic asthma, we investigated the role of LTs in two models of allergic inflammation: intranasal Aspergillus protease allergen and recombinant IL-13-induced T helper type 2 (Th2) cell-mediated inflammation, and also examined Th2-related chemokines downstream of LTs signaling. 5-Lipoxygenase (5-LO)-deficient mice exposed to short-term intranasal Aspergillus protease allergen showed attenuated airway inflammation, decreased airway hyper-responsiveness and reduced bronchoalveolar eosinophilia when compared to wild-type mice. However, this phenotype was less apparent using long exposure to the same allergen. 5-LO-deficient mice exposed to intranasal rIL-13 also showed attenuated phenotypes of allergic asthma via significant reduction in Th2-specific chemokines, CCL7 and CCL17 production and decreased Th2 cells recruitment to the lungs. Addition of leukotriene B4 (LTB4) and LTC4 to the airways of 5-LO-deficient mice resulted in the rescue of rIL-13-induced experimental asthma. Furthermore, LTs addition to rIL-13 synergistically enhanced the production of Th2-specific chemokines in the lung and inflammatory responses. Therefore, our findings suggest that LTs complement allergens and their downstream cytokine (e.g., IL-13) induced Th2 inflammation by enhancing the induction of Th2 chemokines.
    Clinical and experimental medicine. 06/2014;
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    ABSTRACT: Environmental fungi have been linked to TH2 cell-related airway inflammation and the TH2-associated chronic airway diseases asthma, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown.
    The Journal of allergy and clinical immunology. 06/2014;
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    ABSTRACT: Vaccination has been the most widely used strategy to protect against viral infections for centuries. However, the molecular mechanisms governing the long-term persistence of immunological memory in response to vaccines remain unclear. Here we show that autophagy has a critical role in the maintenance of memory B cells that protect against influenza virus infection. Memory B cells displayed elevated levels of basal autophagy with increased expression of genes that regulate autophagy initiation or autophagosome maturation. Mice with B cell-specific deletion of Atg7 (B/Atg7(-/-) mice) showed normal primary antibody responses after immunization against influenza but failed to generate protective secondary antibody responses when challenged with influenza viruses, resulting in high viral loads, widespread lung destruction and increased fatality. Our results suggest that autophagy is essential for the survival of virus-specific memory B cells in mice and the maintenance of protective antibody responses required to combat infections.
    Nature medicine 04/2014; · 27.14 Impact Factor
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    ABSTRACT: Allergic asthma is a chronic inflammatory disease of the airways. Of the different lower airway-infiltrating immune cells that participate in asthma, T lymphocytes that produce Th2 cytokines play important roles in pathogenesis. These T cells are mainly fully-differentiated CCR7- effector memory T (TEM) cells. Targeting TEM cells without affecting CCR7+ naive and central memory (TCM) cells has the potential of treating TEM-mediated diseases, such as asthma, without inducing generalized immunosuppression. The voltage-gated KV1.3 potassium channel is a target for preferential inhibition of TEM cells. Here, we investigated the effects of ShK-186, a selective KV1.3 channel blocker, for the treatment of asthma. A significant proportion of T lymphocytes in the lower airways of subjects with asthma expressed high levels of KV1.3 channels. ShK-186 inhibited the allergen-induced activation of peripheral blood T cells from those subjects. Immunization of F344 rats against ovalbumin, followed by intranasal challenges with ovalbumin, induced airway hyper-reactivity which was reduced by the administration of ShK-186. ShK-186 also reduced total immune infiltrates in the bronchoalveolar lavage and number of infiltrating lymphocytes, eosinophils, and neutrophils assessed by differential counts. Rats with the ovalbumin-induced model of asthma had elevated levels of the Th2 cytokines IL-4, IL-5, and IL-13 measured by ELISA in their bronchoalveolar lavage fluids. ShK-186 administration reduced levels of IL-4 and IL-5 and induced an increase in the production of IL-10. Finally, ShK-186 inhibited the proliferation of lung-infiltrating ovalbumin-specific T cells. Our results suggest that KV1.3 channels represent effective targets for the treatment of allergic asthma.
    Journal of Biological Chemistry 03/2014; · 4.65 Impact Factor
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    ABSTRACT: The development of emphysema in humans and mice exposed to cigarette smoke is promoted by activation of an adaptive immune response. Lung myeloid dendritic cells (mDCs) derived from cigarette smokers activate autoreactive Th1 and Th17 cells. mDC-dependent activation of T cell subsets requires expression of the SPP1 gene, which encodes osteopontin (OPN), a pleiotropic cytokine implicated in autoimmune responses. The upstream molecular events that promote SPP1 expression and activate mDCs in response to smoke remain unknown. Here, we show that peroxisome proliferator-activated receptor γ (PPARG/Pparg) expression was downregulated in mDCs of smokers with emphysema and mice exposed to chronic smoke. Conditional knockout of PPARγ in APCs using Cd11c-Cre Ppargflox/flox mice led to spontaneous lung inflammation and emphysema that resembled the phenotype of smoke-exposed mice. The inflammatory phenotype of Cd11c-Cre Ppargflox/flox mice required OPN, suggesting an antiinflammatory mechanism in which PPARγ negatively regulates Spp1 expression in the lung. A 2-month treatment with a PPARγ agonist reversed emphysema in WT mice despite continual smoke exposure. Furthermore, endogenous PPARγ agonists were reduced in the plasma of smokers with emphysema. These findings reveal a proinflammatory pathway, in which reduced PPARγ activity promotes emphysema, and suggest that targeting this pathway in smokers could prevent and reverse emphysema.
    The Journal of clinical investigation 02/2014; · 15.39 Impact Factor
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    ABSTRACT: Proteinases and the innate immune receptor Toll-like receptor 4 (TLR4) are essential for expression of allergic inflammation and diseases such as asthma. A mechanism that links these inflammatory mediators is essential for explaining the fundamental basis of allergic disease but has been elusive. Here, we demonstrate that TLR4 is activated by airway proteinase activity to initiate both allergic airway disease and antifungal immunity. These outcomes were induced by proteinase cleavage of the clotting protein fibrinogen, yielding fibrinogen cleavage products that acted as TLR4 ligands on airway epithelial cells and macrophages. Thus, allergic airway inflammation represents an antifungal defensive strategy that is driven by fibrinogen cleavage and TLR4 activation. These findings clarify the molecular basis of allergic disease and suggest new therapeutic strategies.
    Science 08/2013; 341(6147):792-6. · 31.20 Impact Factor
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    ABSTRACT: Rationale: Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) or chronic rhinosinusitis with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization respectively, however the pathophysiology of CRS remains unclear. The importance of innate lymphoid cells in Th2-mediated inflammatory disease has not been clearly defined. Objective: The objective of this study was to investigate the role of the epithelial cell-derived cytokine IL-33 and IL-33-responsive innate lymphoid cells in the pathophysiology of chronic rhinosinusitis. Methods: Relative gene expression was evaluated using quantitative real-time PCR. Innate lymphoid cells in inflamed ethmoid sinus mucosa from CRSsNP and CRSwNP patients were characterized using flow cytometry. Cytokine production from lymphoid cells isolated from inflamed mucosa of chronic rhinosinusitis patients was examined using ELISA and intracellular cytokine staining. Measurements and Main Results: Elevated expression of ST2, the ligand binding chain of the IL-33 receptor was observed in inflamed sinonasal mucosa from CRSwNP compared to CRSsNP and healthy control. An increased percentage of innate lymphoid cells was observed in inflamed sinonasal mucosa from CRSwNP compared to CRSsNP. ST2+ innate lymphoid cells are a consistent source of IL-13 in response to IL-33 stimulation. Significant induction of IL-33 was observed in epithelial cells derived from CRSwNP patients compared to CRSsNP patients in response to stimulation with Aspergillus fumigatus extract. Conclusions: These data suggest a role for sinonasal epithelial cell derived IL-33 and an IL-33- responsive innate lymphoid cell population in the pathophysiology of CRSwNP demonstrating the functional importance of innate lymphoid cells in Th2-mediated inflammatory disease.
    American Journal of Respiratory and Critical Care Medicine 06/2013; · 11.04 Impact Factor
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    ABSTRACT: Transcription factors of the STAT family are critical in the cytokine-mediated functional differentiation of CD4(+) helper T cells. Signaling inhibitors of the SOCS family negatively regulate the activation of STAT proteins; however, their roles in the differentiation and function of helper T cells are not well understood. Here we found that the SOCS protein CIS, which was substantially induced by interleukin 4 (IL-4), negatively regulated the activation of STAT3, STAT5 and STAT6 in T cells. CIS-deficient mice spontaneously developed airway inflammation, and CIS deficiency in T cells led to greater susceptibility to experimental allergic asthma. CIS-deficient T cells showed enhanced differentiation into the TH2 and TH9 subsets of helper T cells. STAT5 and STAT6 regulated IL-9 expression by directly binding to the Il9 promoter. Our data thus demonstrate a critical role for CIS in controlling the proallergic generation of helper T cells.
    Nature Immunology 06/2013; · 26.20 Impact Factor
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    ABSTRACT: BACKGROUND: TH2-dependent diseases vary in severity according to genotype, but relevant gene polymorphisms remain largely unknown. The integrin CD11a is a critical determinant of allergic responses, and allelic variants of this gene might influence allergic phenotypes. OBJECTIVE: We sought to determine major CD11a allelic variants in mice and human subjects and their importance to allergic disease expression. METHODS: We sequenced mouse CD11a alleles from C57BL/6 and BALB/c strains to identify major polymorphisms; human CD11a single nucleotide polymorphisms were compared with allergic disease phenotypes as part of the international HapMap project. Mice on a BALB/c or C57BL/6 background and congenic for the other strain's CD11a allele were created to determine the importance of mouse CD11a polymorphisms in vivo and in vitro. RESULTS: Compared with the C57BL/6 allele, the BALB/c CD11a allele contained a nonsynonymous change from asparagine to aspartic acid within the metal ion binding domain. In general, the BALB/c CD11a allele enhanced and the C57BL/6 CD11a allele suppressed TH2 cell-dependent disease caused by the parasite Leishmania major and allergic lung disease caused by the fungus Aspergillus niger. Relative to the C57BL/6 CD11a allele, the BALB/c CD11a allele conferred both greater T-cell adhesion to CD54 in vitro and enhanced TH2 cell homing to lungs in vivo. We further identified a human CD11a polymorphism that significantly associated with atopic disease and relevant allergic indices. CONCLUSIONS: Polymorphisms in CD11a critically influence TH2 cell homing and diverse TH2-dependent immunopathologic states in mice and potentially influence the expression of human allergic disease.
    The Journal of allergy and clinical immunology 05/2013; · 12.05 Impact Factor
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    ABSTRACT: ABSTRACT Although the effects of the interleukin 13 (IL-13) on goblet cell (GC) hyperplasia have been studied in the gut and respiratory tracts, its effect on regulating conjunctival GC has not been explored. The purpose of this study was to determine the major IL-13-producing cell type and the role of IL-13 in GC homeostasis in normal murine conjunctiva. Using isolating techniques, we identified natural killer (NK)/natural killer T (NKT) cells as the main producers of IL-13. We also observed that IL-13 knockout (KO) and signal transducer and activator of transcription 6 knockout (STAT6KO) mice had a lower number of periodic acid Schiff (PAS)+GCs. We observed that desiccating stress (DS) decreases NK population, GCs, and IL-13, whereas it increases interferon-γ (IFN-γ) mRNA in conjunctiva. Cyclosporine A treatment during DS maintained the number of NK/NKT cells in the conjunctiva, increased IL-13 mRNA in NK+ cells, and decreased IFN-γ and IL-17A mRNA transcripts in NK+ and NK- populations. C57BL/6 mice chronically depleted of NK/NKT cells, as well as NKT cell-deficient RAG1KO and CD1dKO mice, had fewer filled GCs than their wild-type counterparts. NK depletion in CD1dKO mice had no further effect on the number of PAS+ cells. Taken together, these findings indicate that NKT cells are major sources of IL-13 in the conjunctival mucosa that regulates GC homeostasis.
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    ABSTRACT: The DNA binding protein methyl-CpG binding protein 2 (MeCP2) critically influences neuronal and brain function by modulating gene expression, and children with overexpression of the MECP2 gene exhibit postnatal neurological syndromes. We demonstrate that some children with MECP2 duplication also display variable immunological abnormalities that include reductions in memory T and B cells and natural killer cells and immunoglobulin assay responses. Moreover, whereas mice with MeCP2 overexpression were unable to control infection with the intra-macrophage parasite Leishmania major and secrete interferon-γ (IFN-γ) from involved lymph nodes, they were able to control airway fungal infection by Aspergillus niger and mount protective T helper cell type 2 (T(H)2)-dependent allergic responses. Relative to normal T cells, T(H) cells from children and mice with MECP2 duplication displayed similar impairments in IFN-γ secretion and T(H)1 responses that were due to both MeCP2-dependent suppression of IFN-γ transcription and sequestration of the IFN-γ locus as assessed by chromatin immunoprecipitation assay. Thus, overexpressed MeCP2 aberrantly suppresses IFN-γ secretion from T(H) cells, potentially leading to a partially immunodeficient state. Our findings establish a rational basis for identifying, treating, and preventing infectious complications potentially affecting children with MECP2 duplication.
    Science translational medicine 12/2012; 4(163):163ra158. · 10.76 Impact Factor
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    ABSTRACT: The etiology of status asthmaticus (SA), a complication of severe asthma, is unknown. Fungal exposure, as measured by fungal atopy, is a major risk factor for developing asthma, but the relationship of fungi in SA per se has not previously been reported. In this five patient retrospective case series study, lower respiratory tract cultures were performed on bronchoalveolar lavage or tracheal aspirate fluid, comparing standard clinical laboratory cultures with a specialized technique in which respiratory mucus was removed prior to culture. We show that mucolytic treatment allows an increased detection of fungal growth, especially yeast, from the lower airways of all SA patients. We also demonstrate that inhalation of the yeast Candida albicans readily induces asthma-like disease in mice. Our observations suggest that SA may represent a fungal infectious process, and support additional prospective studies utilizing anti-fungal therapy to supplement conventional therapy, broad-spectrum antibiotics and high-dose glucocorticoids, which can promote fungal overgrowth.
    Clinical Immunology 11/2012; 146(2):77-83. · 3.77 Impact Factor
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    Sumanth Polikepahad, David B Corry
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    ABSTRACT: RNA interference mediated through antisense transcripts is a fundamentally important mechanism regulating gene expression that remains incompletely understood. Here, we have used next-generation sequencing to determine from mouse CD4+ T cells the functional implications of antisense transcripts binding to argonaute (AGO) proteins that mediate RNA interference and post-transcriptional gene silencing. This effort identified 90 new microRNAs (miRNAs) and six endogenous hairpin RNA-derived small interfering RNAs (siRNAs) mapping to distinct introns. Unexpectedly, 69 miRNAs were expressed as non-canonical isomiRs as the dominant AGO-binding transcript, with extensive 3' terminal nucleotide modifications. Furthermore, differential expression analysis between AGO1- and AGO2-bound miRNAs suggested preferential binding of isomiRs ending with 3' adenine residues to AGO1 and 3' uridine residues to AGO2. Analysis of the putative targets of all miRNAs suggested a striking preference for regulating transcription and transcription factors with additional evidence of a functional division of labor between AGO proteins in this regard. We further provide evidence that multiple mitochondrial genomic loci serve as the source of endogenous cis-natural antisense transcripts. These findings imply diversity in AGO protein function based on differential miRNA binding and indicate that RNA interference-based gene regulation is more complex than previously recognized.
    Nucleic Acids Research 11/2012; · 8.81 Impact Factor
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    ABSTRACT: SESSION TYPE: Asthma PostersPRESENTED ON: Wednesday, October 24, 2012 at 01:30 PM - 02:30 PMPURPOSE: Status asthmaticus (SA) is an acute exacerbation of asthma and similar to conventional asthma, SA is thought to be induced through inhalational exposure to allergens including molds. The purpose of this study is to explore if fungi play a role in SA through identification of lower respiratory tract pathogens of intubated patients and determine if a fungal isolate can elicit allergic lung disease in mice.METHODS: Clinical information was retrospectively obtained on five SA patients admitted to the Ben Taub General Hospital medical intensive care unit. Lower airway secretions by bronchoalveolar lavage or tracheal aspiration were obtained. Lower airway samples were processed using standard culture techniques and in parallel underwent specialized processing to remove mucus and cells prior to culture. The ability of a clinical isolate of Candida albicans, a yeast, found in all patient airway cultures to induce allergic lung disease in C57BL/6 mice was assessed.RESULTS: Fungi were cultured from lower respiratory specimens in 2 out of 5 patients by standard culture techniques. In contrast, after removal of respiratory mucus, filamentous fungi (molds) were identified from three patients and heavy growth of yeast (Candida spp.) was found from all sample cultures. All patients received intravenous corticosteroids and broad-spectrum antibiotics. Mice exposed to intranasal C. albicans developed significant increases in airway hyperreactivity, BAL fluid eosinophilia and a dose-dependent predominance of lung IL-4 and IL-17A compared to controls.CONCLUSIONS: Tracheobronchial mycoses was observed in a cohort of SA patients. An improved method of culture technique involving the removal of mucus is superior to standard culture techniques in revealing fungi in respiratory samples. An isolate of C. albicans elicited profound allergic inflammation and airway hyperreactivity similar to asthma-like disease when given intranasally to mice.CLINICAL IMPLICATIONS: Combined use of glucocorticoids and broad-spectrum antibiotics may contribute to tracheobronchial mycoses and may have potential to cause or exacerbate fungal overgrowth in asthma. Treatment with anti-fungal antibiotics and avoidance of therapies that promote fungal overgrowth should be considered in the management of SA.DISCLOSURE: The following authors have nothing to disclose: Garbo Mak, Paul Porter, Venkata Bandi, Amber Luong, Farrah Kheradmand, David CorryWe removed mucus and cells from respiratory specimens prior to fungal culture on Sabourand plates by processing samples with dithiothreitol. This step helps remove fungicidal mucus that surrounds pathogens found in the airway, thereby optimizing fungal culture growth. This process is not performed in standard fungal cultures.Baylor College of Medicine, Houston, TX.
    Chest 10/2012; 142(4_MeetingAbstracts):701A. · 7.13 Impact Factor
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    ABSTRACT: This is a concise review on Interleukin (IL)-13 and the evolution of asthma therapy, from discovery of the molecule, the identification of its pathogenic role in animal models of asthma, to the development of clinically successful neutralizing agents. The translational path from basic research to clinical application was not sequential as expected but random with respect to the tools (molecular & cell biology, animal models, human studies) used and to the application of academic versus industry research. The experiences with the development of neutralizing anti-IL-13 reagents emphasize the need for inclusion of a biomarker assay in the clinical trials that both identifies individuals that actually have aberrant expression of the pathway of interest and allows determining whether the target of interest is neutralized.
    American journal of clinical and experimental immunology. 06/2012; 1(1):20-27.
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    William T Shearer, David B Corry
    The Journal of allergy and clinical immunology 03/2012; 129(3):715-6. · 12.05 Impact Factor
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    ABSTRACT: Over the past few decades, neutrophils and macrophages had co-occupied center stage as the critical innate immune cells underlying the pathobiology of cigarette smoke-induced chronic obstructive pulmonary disease and lung parenchymal destruction (i.e., emphysema). While chronic exposure to smoke facilitates the recruitment of innate immune cells into the lung, a clear role for adaptive immunity in emphysema has emerged. Evidence from human studies specifically point to a role for recruitment and activation of pathogenic lymphocytes and lung antigen-presenting cells in emphysema; similarly, animal models have confirmed a significant role for autoimumnity in progressive smoke-induced emphysema. Increased numbers of activated antigen-presenting cells, Th1 and Th17 cells, have been associated with smoke-induced lung inflammation and production of the canonical cytokines of these cells, IFN-γ and IL-17, correlates with disease severity. These exciting new breakthroughs could open new avenues for developing effective new therapies for smoke-induced emphysema.
    Expert Review of Clinical Immunology 03/2012; 8(3):285-92. · 2.89 Impact Factor
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    ABSTRACT: Smoking-related lung diseases are among the leading causes of death worldwide, underscoring the need to understand their pathogenesis and develop new effective therapies. We have shown that CD1a+ antigen-presenting cells (APCs) from lungs of patients with emphysema can induce autoreactive T helper 1 (T(H)1) and T(H)17 cells. Similarly, the canonical cytokines interferon-γ (IFN-γ) and interleukin-17A (IL-17A) are specifically linked to lung destruction in smokers, but how smoke activates APCs to mediate emphysema remains unknown. Here, we show that, in addition to increasing IFN-γ expression, cigarette smoke increased the expression of IL-17A in both CD4+ and γδ T cells from mouse lung. IL-17A deficiency resulted in attenuation of, whereas lack of γδ T cells exacerbated, smoke-induced emphysema in mice. Adoptive transfer of lung APCs isolated from mice with emphysema revealed that this cell population was capable of transferring disease even in the absence of active smoke exposure, a process that was dependent on IL-17A expression. Spp1 (the gene for osteopontin) was highly expressed in the pathogenic lung APCs of smoke-exposed mice and was required for the T(H)17 responses and emphysema in vivo, in part through its inhibition of the expression of the transcription factor Irf7. Thus, the Spp1-Irf7 axis is critical for induction of pathological T(H)17 responses, revealing a major mechanism by which smoke activates lung APCs to induce emphysema and identifying a pathway that could be targeted for therapeutic purposes.
    Science translational medicine 01/2012; 4(117):117ra9. · 10.76 Impact Factor
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    ABSTRACT: A series of epidemiologic studies have identified the fungus Alternaria as a major risk factor for asthma. The airway epithelium plays a critical role in the pathogenesis of allergic asthma. These reports suggest that activated airway epithelial cells can produce cytokines such as IL-25, TSLP and IL-33 that induce Th2 phenotype. However the epithelium-derived products that mediate the pro-asthma effects of Alternaria are not well characterized. We hypothesized that exposure of the airway epithelium to Alternaria releasing cytokines that can induce Th2 differentiation. We used ELISA to measure human and mouse cytokines. Alternaria extract (ALT-E) induced rapid release of IL-18, but not IL-4, IL-9, IL-13, IL-25, IL-33, or TSLP from cultured normal human bronchial epithelial cells; and in the BAL fluids of naïve mice after challenge with ALT-E. Both microscopic and FACS indicated that this release was associated with necrosis of epithelial cells. ALT-E induced much greater IL-18 release compared to 19 major outdoor allergens. Culture of naïve CD4 cells with rmIL-18 induced Th2 differentiation in the absence of IL-4 and STAT6, and this effect was abrogated by disrupting NF- κB p50 or with a NEMO binding peptide inhibitor. Rapid and specific release of IL-18 from Alternaria-exposed damaged airway epithelial cells can directly initiate Th2 differentiation of naïve CD4(+) T-cells via a unique NF-κB dependent pathway.
    PLoS ONE 01/2012; 7(2):e30280. · 3.53 Impact Factor
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    ABSTRACT: Cross-sectional studies have suggested a role for activation of adaptive immunity in smokers with emphysema, but the clinical application of these findings has not been explored. Here we examined the utility of detecting autoreactive T cells as a screening tool for emphysema in an at-risk population of smokers. We followed 156 former and current (ever)-smokers for 2 years to assess whether peripheral blood CD4 T cell cytokine responses to lung elastin fragments (EFs) could discriminate between those with and without emphysema, and to evaluate the relevance of autoreactive T cells to predict changes during follow-up in lung physiological parameters. Volunteers underwent baseline complete phenotypic assessment with pulmonary function tests, quantitative chest CT, yearly 6-min walk distance (6MWD) testing, and annual measurement of CD4 T cell cytokine responses to EFs. The areas under the receiver operating characteristic curve to predict emphysema for interferon gamma (IFN-γ), and interleukin 6 (IL-6) responses to EFs were 0.81 (95% CI of 0.74-0.88) and 0.79 (95% CI of 0.72-0.86) respectively. We developed a dual cytokine enzyme-linked immunocell spot assay, the γ-6 Spot, using CD4 T cell IFN-γ and IL-6 responses and found that it discriminated emphysema with 90% sensitivity. After adjusting for potential confounders, the presence of autoreactive T cells was predictive of a decrease in 6MWD over 2 years (decline in 6MWD, -19 m per fold change in IFN-γ; P = 0.026, and -26 m per fold change in IL-6; P = 0.003). In support of the human association studies, we cloned CD4 T cells with characteristic T helper (Th)1 and Th17 responses to EFs in the peripheral blood of ever-smokers with emphysema, confirming antigenicity of lung elastin in this population. These findings collectively suggest that the EF-specific autoreactive CD4 T cell assay, γ-6 Spot, could provide a non-invasive diagnostic tool with potential application to large-scale screening to discriminate emphysema in ever-smokers, and predict early relevant physiological outcomes in those at risk.
    Frontiers in Immunology 01/2012; 3:267.

Publication Stats

6k Citations
969.13 Total Impact Points

Institutions

  • 1999–2014
    • Baylor College of Medicine
      • • Department of Medicine
      • • Department of Pathology & Immunology
      Houston, Texas, United States
  • 2013
    • University of Texas Medical School
      • Department of Otorhinolaryngology-Head & Neck Surgery
      Houston, Texas, United States
  • 2007–2013
    • University of Texas MD Anderson Cancer Center
      • Department of Immunology
      Houston, TX, United States
    • University of Texas Health Science Center at Houston
      • Medical School
      Houston, TX, United States
  • 2006
    • Houston Methodist Hospital
      Houston, Texas, United States
  • 2002
    • Australian National University
      Canberra, Australian Capital Territory, Australia
  • 2000
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 1993–2000
    • University of California, San Francisco
      • • Department of Microbiology and Immunology
      • • Division of Hospital Medicine
      San Francisco, CA, United States
  • 1996
    • J. David Gladstone Institutes
      San Francisco, California, United States