David B Corry

Baylor College of Medicine, Houston, Texas, United States

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Publications (114)1042.63 Total impact

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    ABSTRACT: Objective: Angiogenesis is tightly controlled by growth factors and cytokines in pathophysiological settings. Interleukin 37 (IL-37) is a newly identified cytokine of the IL-1 family, some members of which are important in inflammation and angiogenesis. However, the function of IL-37 in angiogenesis remains unknown. We aimed to explore the regulatory role of IL-37 in pathological and physiological angiogenesis. Approach and results: We found that IL-37 was expressed and secreted in endothelial cells and upregulated under hypoxic conditions. IL-37 enhanced endothelial cell proliferation, capillary formation, migration, and vessel sprouting from aortic rings with potency comparable with that of vascular endothelial growth factor. IL-37 activates survival signals including extracellular signal-regulated kinase 1/2 and AKT in endothelial cells. IL-37 promoted vessel growth in implanted Matrigel plug in vivo in a dose-dependent manner with potency comparable with that of basic fibroblast growth factor. In the mouse model of retinal vascular development, neonatal mice administrated with IL-37 displayed increased neovascularization. We demonstrated further that IL-37 promoted pathological angiogenesis in the mouse model of oxygen-induced retinopathy. Conclusions: Our findings suggest that IL-37 is a novel and potent proangiogenic cytokine with essential role in pathophysiological settings.
    Arteriosclerosis Thrombosis and Vascular Biology 10/2015; DOI:10.1161/ATVBAHA.115.306543 · 6.00 Impact Factor
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    ABSTRACT: Signal transducer and activator of transcription 6 (STAT6) transmits signals from cytokines IL-4 and IL-13 and is activated in allergic airway disease. We are developing phosphopeptide mimetics targeting the SH2 domain of STAT6 to block recruitment to phosphotyrosine residues on IL-4 or IL-13 receptors and subsequent Tyr641 phosphorylation to inhibit the expression of genes contributing to asthma. Structure-affinity relationship studies showed that phosphopeptides based on Tyr631 from IL-4Rα bind with weak affinity to STAT6 whereas replacing the pY+3 residue with simple aryl and alkyl amides resulted in affinities in the mid to low nM range. A set of phosphatase-stable, cell-permeable prodrug analogs inhibited cytokine-stimulated STAT6 phosphorylation in both Beas-2B human airway cells and primary mouse T-lymphocytes at concentrations as low as 100 nM. IL-13-stimulated expression of CCL26 (eotaxin-3) was inhibited in a dose-dependent manner, demonstrating that targeting the SH2 domain blocks both phosphorylation and transcriptional activity of STAT6.
    Journal of Medicinal Chemistry 10/2015; DOI:10.1021/acs.jmedchem.5b01321 · 5.45 Impact Factor
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    ABSTRACT: Smoking-related emphysema is a chronic inflammatory disease driven by the TH17 subset of helper T cells through molecular mechanisms that remain obscure. Here we explored the role of the microRNA miR-22 in emphysema. We found that miR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism that involved the transcription factor NF-κB. Mice deficient in miR-22, but not wild-type mice, showed attenuated TH17 responses and failed to develop emphysema after exposure to smoke or nCB. We further found that miR-22 controlled the activation of APCs and TH17 responses through the activation of AP-1 transcription factor complexes and the histone deacetylase HDAC4. Thus, miR-22 is a critical regulator of both emphysema and TH17 responses.
    Nature Immunology 10/2015; DOI:10.1038/ni.3292 · 20.00 Impact Factor
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    ABSTRACT: Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. Here we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c(+) lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema, and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.
    eLife Sciences 10/2015; 4. DOI:10.7554/eLife.09623 · 9.32 Impact Factor
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    ABSTRACT: Cross-sectional studies of T cell responses to self-antigens correlate with baseline emphysema severity. We investigated whether clinical and or immunological factors could predict disease progression such as emphysema, FEV1, 6-minute walk distance (6MWD), in former and active smokers in a 5-year prospective study. We recruited 224 ever smokers over 40 years of age and with greater than a15-pack year smoking history. Repeated spirometry, 6MWD, and peripheral blood T cell cytokine responses to lung elastin fragments were measured. Baseline and repeat chest CT (34 to 65 months apart) were used to quantify emphysema progression. Of the 141 ever smokers with baseline and repeat CT scans, the mean (standard deviation) annual rate of change in percent emphysema was +0.46 (0.92), ranging from -1.8 to +4.1. In multivariable analyses, the rate of emphysema progression was greater in subjects who had lower body mass index (BMI) (+0.15 per 5 unit decrease in BMI, 95%CI, +0.03 to +0.29). In active smokers, increased IFN-γ and IL-6 T cell responses had a positive association with the annual rate of emphysema progression. Male gender and IL-6 T cell responses to elastin fragments were significantly associated with annual 6MWD decline, while IL-13 was associated with an increase in annual 6MWD. The rate of emphysema progression quantified by CT scans among ever smokers was highly variable; clinical factors and biomarkers explained only some of the variability. Aggressive clinical care that targets active smokers with autoreactive T cells, hypertension or low BMI may temporize progression of emphysema.
    American Journal of Respiratory and Critical Care Medicine 08/2015; DOI:10.1164/rccm.201504-0736OC · 13.00 Impact Factor
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    ABSTRACT: To investigate the effects of IL-13 on goblet cell proliferation, differentiation, and expression of mucin and immunomodulatory genes. Explants were excised from the conjunctiva of young C57BL/6 mice. Cultures received 200 μL per week of either Keratinocyte media (KSFM) or KSFM supplemented with 10 ng/mL IL-13 and were incubated for 3 (D3), 7 (D7), or 14 (D14) days. Subsequently, cell proliferation was assessed or cultures were immunostained, collected for dot blot, or for reverse transcription (RT) and quantitative real-time PCR (qPCR) or for RT-PCR gene array. The cultured conjunctival epithelium expressed goblet cell associated keratin 7 and mucins MUC5AC and MUC2 and when stimulated with IL-13 showed increased proliferation at D3 and D7 (P < 0.05) compared with control. MUC5AC expression was increased in the IL-13-treated group at D3 and D14 (P < 0.05). IL-13-treated cultures showed increased chemokine ligand 26 (CCL26), chloride channel calcium activated channel 3 (CLCA3), fas ligand (FasL), and Relm-β at D7. All conjunctival cultures expressed MUC2, and its expression was decreased at D3 (P < 0.05) and increased at D14 (P < 0.05) with IL-13 treatment. This study demonstrated that conjunctival goblet cells are IL-13 responsive cells that produce factors known to maintain epithelial barrier, stimulate mucin production, and modulate immune response in nonocular mucosa when treated with IL-13. The functional significance of IL-13-stimulated factors remains to be determined.
    Investigative ophthalmology & visual science 07/2015; 56(8):4186-97. DOI:10.1167/iovs.14-15496 · 3.40 Impact Factor
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    ABSTRACT: Micro- and nanometer-size particles have become popular candidates for cancer vaccine adjuvants. However, the mechanism by which such particles enhance immune responses remains unclear. Here, we report a porous silicon microparticle (PSM)-based cancer vaccine that greatly enhances cross-presentation and activates type I interferon (IFN-I) response in dendritic cells (DCs). PSM-loaded antigen exhibited prolonged early endosome localization and enhanced cross-presentation through both proteasome- and lysosome-dependent pathways. Phagocytosis of PSM by DCs induced IFN-I responses through a TRIF- and MAVS-dependent pathway. DCs primed with PSM-loaded HER2 antigen produced robust CD8 T cell-dependent anti-tumor immunity in mice bearing HER2+ mammary gland tumors. Importantly, this vaccination activated the tumor immune microenvironment with elevated levels of intra-tumor IFN-I and MHCII expression, abundant CD11c+ DC infiltration, and tumor-specific cytotoxic T cell responses. These findings highlight the potential of PSM as an immune adjuvant to potentiate DC-based cancer immunotherapy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 04/2015; 11(6). DOI:10.1016/j.celrep.2015.04.009 · 8.36 Impact Factor

  • Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB53. DOI:10.1016/j.jaci.2014.12.1106 · 11.48 Impact Factor
  • Hui-Ying Tung · Cameron Landers · Yuping Qian · Luz Roberts · David B. Corry ·

    Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB391. DOI:10.1016/j.jaci.2014.12.1904 · 11.48 Impact Factor
  • Wen Lu · David B. Corry · Farrah Kheradmand ·

    Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB382. DOI:10.1016/j.jaci.2014.12.1877 · 11.48 Impact Factor
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    ABSTRACT: Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6.
    Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB381. DOI:10.1016/j.jaci.2014.12.1875 · 11.48 Impact Factor
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    ABSTRACT: Exposure to cigarette smoke can initiate sterile inflammatory responses in the lung and activate myeloid dendritic cells (mDCs) that induce differentiation of T helper type 1 (Th1) and Th17 cells in the emphysematous lungs. Consumption of complement proteins increases in acute inflammation, but the contribution of complement protein 3 (C3) to chronic cigarette smoke-induced immune responses in the lung is not clear. Here, we show that following chronic exposure to cigarette smoke, C3-deficient (C3(-/-)) mice develop less emphysema and have fewer CD11b(+)CD11c(+) mDCs infiltrating the lungs as compared with wild-type mice. Proteolytic cleavage of C3 by neutrophil elastase releases C3a, which in turn increases the expression of its receptor (C3aR) on lung mDCs. Mice deficient in the C3aR (C3ar(-/-)) partially phenocopy the attenuated responses to chronic smoke observed in C3(-/-) mice. Consistent with a role for C3 in emphysema, C3 and its active fragments are deposited on the lung tissue of smokers with emphysema, and smoke-exposed mice. Together, these findings suggest a critical role for C3a through autocrine/paracrine induction of C3aR in the pathogenesis of cigarette smoke-induced sterile inflammation and provide new therapeutic targets for the treatment of emphysema.Mucosal Immunology advance online publication, 3 December 2014; doi:10.1038/mi.2014.118.
    Mucosal Immunology 12/2014; 8(4). DOI:10.1038/mi.2014.118 · 7.37 Impact Factor
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    ABSTRACT: The past 15 years of allergic disease research have produced extraordinary improvements in our understanding of the pathogenesis of airway allergic diseases such as asthma. Whereas it was previously viewed as largely an immunoglobulin E-mediated process, the gradual recognition that T cells, especially Type 2 T helper (Th2) cells and Th17 cells, play a major role in asthma and related afflictions has inspired clinical trials targeting cytokine-based inflammatory pathways that show great promise. What has yet to be clarified about the pathogenesis of allergic inflammatory disorders, however, are the fundamental initiating factors, both exogenous and endogenous, that drive and sustain B- and T-cell responses that underlie the expression of chronic disease. Here we review how proteinases derived from diverse sources drive allergic responses. A central discovery supporting the proteinase hypothesis of allergic disease pathophysiology is the role played by airway fibrinogen, which in part appears to serve as a sensor of unregulated proteinase activity and which, when cleaved, both participates in a novel allergic signaling pathway through Toll-like receptor 4 and forms fibrin clots that contribute to airway obstruction. Unresolved at present is the ultimate source of airway allergenic proteinases. From among many potential candidates, perhaps the most intriguing is the possibility such enzymes derive from airway fungi. Together, these new findings expand both our knowledge of allergic disease pathophysiology and options for therapeutic intervention.
    12/2014; 11(Supplement 5):S277-S283. DOI:10.1513/AnnalsATS.201403-105AW
  • Michael E. Scheurer · E Susan Amirian · Paul Porter · David B. Corry ·

    Cancer Research 10/2014; 74(19 Supplement):4163-4163. DOI:10.1158/1538-7445.AM2014-4163 · 9.33 Impact Factor
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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; 15(3). DOI:10.1007/s10238-014-0292-7 · 2.96 Impact Factor
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    ABSTRACT: Background: Environmental fungi have been linked to T(H)2 cell-related airway inflammation and the T(H)2-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. Objective: To determine the frequency of fungus isolation and fungus-specific immunity in patients with T(H)2-associated and non-T(H)2-associated airway disease. Methods: Sinus lavage fluid and blood were collected from sinus surgery patients (n = 118) including patients with CRSwNP, patients with CRS without nasal polyps, patients with AFRS, and non-CRS/nonasthmatic control patients. Asthma status was determined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. PBMCs were restimulated with fungal antigens in an enzyme-linked immunocell spot assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared with fungus-specific IgE levels measured from plasma by ELISA. Results: Filamentous fungi were significantly more commonly cultured in patients with T(H)2-associated airway disease (asthma, CRSwNP, or AFRS: n = 68) than in control patients with non-T(H)2-associated disease (n = 31): 74% vs 16%, respectively (P < .001). Both fungus-specific IL-4 enzyme-linked immunocell spot (n = 48) and specific IgE (n = 70) data correlated with T(H)2-associated diseases (sensitivity 73% and specificity 100% vs 50% and 77%, respectively). Conclusions: The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with T(H)2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients.
    Journal of Allergy and Clinical Immunology 06/2014; 134(2). DOI:10.1016/j.jaci.2014.04.028 · 11.48 Impact Factor
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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; 20(5). DOI:10.1038/nm.3521 · 27.36 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; 289(18). DOI:10.1074/jbc.M113.517037 · 4.57 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; 124(3). DOI:10.1172/JCI70587 · 13.22 Impact Factor

  • Journal of Allergy and Clinical Immunology 02/2014; 133(2):AB178. DOI:10.1016/j.jaci.2013.12.637 · 11.48 Impact Factor

Publication Stats

4k Citations
1,042.63 Total Impact Points


  • 1999-2015
    • Baylor College of Medicine
      • • Department of Pathology & Immunology
      • • Department of Medicine
      Houston, Texas, United States
  • 2013
    • University of Texas MD Anderson Cancer Center
      • Department of Immunology
      Houston, TX, United States
  • 1997-2011
    • University of California, San Francisco
      • • Lung Biology Center
      • • Division of Hospital Medicine
      San Francisco, CA, United States
  • 2006
    • Houston Methodist Hospital
      Houston, Texas, United States