D P Huston

Texas A&M University System Health Science Center, Bryan, TX, United States

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Publications (72)515.09 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Basophils have emerged in recent years as a small but potent subpopulation of leukocytes capable of bridging innate and adaptive immunity. They can be activated through IgE-dependent and IgE-independent mechanisms to release preformed mediators and to produce Th2 cytokines. In addition to their role in protective immunity to helminths, basophils are major participants in allergic reactions as diverse as anaphylaxis and immediate hypersensitivity reactions, late-phase hypersensitivity reactions, and delayed hypersensitivity reactions. Additionally, basophils have been implicated in the pathophysiology of autoimmune diseases such as lupus nephritis and rheumatoid arthritis, and the modulation of immune responses to bacterial infections, as well as being a feature of myelogenous leukemias. Distinct signals for activation, degranulation, transendothelial migration, and immune regulation are being defined, and demonstrate the important role of basophils in promoting a Th2 microenvironment. These mechanistic insights are driving innovative approaches for diagnostic testing and therapeutic targeting of basophils.
    Current Allergy and Asthma Reports 01/2014; 14(1):408. · 2.75 Impact Factor
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    ABSTRACT: The eosinophil is a multifunctional granulocyte best known for providing host defense against parasites. Paradoxically, eosinophils are also implicated in the pathogenesis of allergic inflammation, asthma, and hypereosinophilic syndromes. Emerging evidence also supports the potential for harnessing the cytotoxic power of eosinophils and redirecting it to kill solid tumors. Central to eosinophil physiology is interleukin-5 (IL-5) and its receptor (IL-5R) which is composed of a ligand-specific alpha chain (IL-5Rα) and the common beta chain (βc). Eosinophil activation can lead to their degranulation, resulting in rapid release of an arsenal of tissue-destructive proinflammatory mediators and cytotoxic proteins that can be both beneficial and detrimental to the host. This review discusses eosinophil immunobiology and therapeutic strategies for targeting of IL-5 and IL-5R, as well as the potential for harnessing eosinophil cytotoxicity as a tumoricide.
    Current Allergy and Asthma Reports 08/2012; 12(5):402-12. · 2.75 Impact Factor
  • David P Huston
    Current Allergy and Asthma Reports 07/2011; 11(5):342-4. · 2.75 Impact Factor
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    ABSTRACT: The inflammatory cytokine interleukin (IL)-17 is involved in the pathogenesis of allergic diseases. However, the identity and functions of IL-17-producing T cells during the pathogenesis of allergic diseases remain unclear. Here, we report a novel subset of T(H)2 memory/effector cells that coexpress the transcription factors GATA3 and RORγt and coproduce T(H)17 and T(H)2 cytokines. Classical T(H)2 memory/effector cells had the potential to produce IL-17 after stimulation with proinflammatory cytokines IL-1β, IL-6, and IL-21. The number of IL-17-T(H)2 cells was significantly increased in blood of patients with atopic asthma. In a mouse model of allergic lung diseases, IL-17-producing CD4(+) T(H)2 cells were induced in the inflamed lung and persisted as the dominant IL-17-producing T cell population during the chronic stage of asthma. Treating cultured bronchial epithelial cells with IL-17 plus T(H)2 cytokines induced strong up-regulation of chemokine eotaxin-3, Il8, Mip1b, and Groa gene expression. Compared with classical T(H)17 and T(H)2 cells, antigen-specific IL-17-producing T(H)2 cells induced a profound influx of heterogeneous inflammatory leukocytes and exacerbated asthma. Our findings highlight the plasticity of T(H)2 memory cells and suggest that IL-17-producing T(H)2 cells may represent the key pathogenic T(H)2 cells promoting the exacerbation of allergic asthma.
    Journal of Experimental Medicine 10/2010; 207(11):2479-91. · 13.91 Impact Factor
  • Julie Y Patel, Sapandeep K Singh, David P Huston
    Current Allergy and Asthma Reports 09/2010; 10(5):303-5. · 2.75 Impact Factor
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    ABSTRACT: Pulmonary alveolar proteinosis (PAP) is a rare disease of the lung characterized by the accumulation of surfactant-derived lipoproteins within pulmonary alveolar macrophages and alveoli, resulting in respiratory insufficiency and increased infections. The disease is caused by a disruption in surfactant catabolism by alveolar macrophages due to loss of functional granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. The underlying molecular mechanisms causing deficiencies in GM-CSF signaling are as follows: 1) high levels of neutralizing GM-CSF autoantibodies observed in autoimmune PAP; 2) mutations in CSF2RA, the gene encoding the alpha chain of the GM-CSF receptor, observed in hereditary PAP; and 3) reduced numbers and function of alveolar macrophages as a result of other clinical diseases seen in secondary PAP. Recent studies investigating the biology of GM-CSF have revealed that not only does this cytokine have an indispensable role in lung physiology, but it is also a critical regulator of innate immunity and lung host defense.
    Current Allergy and Asthma Reports 09/2010; 10(5):320-5. · 2.75 Impact Factor
  • Ashwini Komarla, Julie Y. Patel, David P. Huston
    Current Allergy and Asthma Reports 09/2009; 9(5):335-336. · 2.45 Impact Factor
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    ABSTRACT: Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. The importance of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of PAP has been confirmed in humans and mice, wherein GM-CSF signaling is required for pulmonary alveolar macrophage catabolism of surfactant. PAP is caused by disruption of GM-CSF signaling in these cells, and is usually caused by neutralizing autoantibodies to GM-CSF or is secondary to other underlying diseases. Rarely, genetic defects in surfactant proteins or the common β chain for the GM-CSF receptor (GM-CSFR) are causal. Using a combination of cellular, molecular, and genomic approaches, we provide the first evidence that PAP can result from a genetic deficiency of the GM-CSFR α chain, encoded in the X-chromosome pseudoautosomal region 1.
    Journal of Experimental Medicine 12/2008; · 13.91 Impact Factor
  • Current Allergy and Asthma Reports 09/2008; 8(5). · 2.45 Impact Factor
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    ABSTRACT: Interleukin (IL) 25 (IL-17E), a distinct member of the IL-17 cytokine family, plays important roles in evoking T helper type 2 (Th2) cell-mediated inflammation that features the infiltrations of eosinophils and Th2 memory cells. However, the cellular sources, target cells, and underlying mechanisms remain elusive in humans. We demonstrate that human Th2 memory cells expressing distinctive levels of IL-25 receptor (R) are one of the responding cell types. IL-25 promotes cell expansion and Th2 cytokine production when Th2 central memory cells are stimulated with thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs), homeostatic cytokines, or T cell receptor for antigen triggering. The enhanced functions of Th2 memory cells induced by IL-25 are associated with sustained expression of GATA-3, c-MAF, and JunB in an IL-4-independent manner. Although keratinocytes, mast cells, eosinophils, and basophils express IL-25 transcripts, activated eosinophils and basophils from normal and atopic subjects were found to secrete bioactive IL-25 protein, which augments the functions of Th2 memory cells. Elevated expression of IL-25 and IL-25R transcripts was observed in asthmatic lung tissues and atopic dermatitis skin lesions, linking their possible roles with exacerbated allergic disorders. Our results provide a plausible explanation that IL-25 produced by innate effector eosinophils and basophils may augment the allergic inflammation by enhancing the maintenance and functions of adaptive Th2 memory cells.
    Journal of Experimental Medicine 09/2007; 204(8):1837-47. · 13.91 Impact Factor
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    ABSTRACT: IL-5, IL-3, and GM-CSF are related hematopoietic cytokines, which regulate the function of myeloid cells and are mediators of the allergic inflammatory response. These cytokines signal through heteromeric receptors containing a specific alpha chain and a shared signaling chain, betac. Previous studies demonstrated that the ubiquitin (Ub) proteasome degradation pathway was involved in signal termination of the betac-sharing receptors. In this study, the upstream molecular events leading to proteasome degradation of the IL-5 receptor (IL-5R) were examined. By using biochemical and flow cytometric methods, we show that JAK kinase activity is required for betac ubiquitination and proteasome degradation but only partially required for IL-5R internalization. Furthermore, we demonstrate the direct ubiquitination of the betac cytoplasmic domain and identify lysine residues 566 and 603 as sites of betac ubiquitination. Lastly, we show that ubiquitination of the betac cytoplasmic domain begins at the plasma membrane, increases after receptor internalization, and is degraded by the proteasome after IL-5R internalization. We propose an updated working model of IL-5R down-regulation, whereby IL-5 ligation of its receptor activates JAK2/1 kinases, resulting in betac tyrosine phosphorylation, ubiquitination, and IL-5R internalization. Once inside the cell, proteasomes degrade the betac cytoplasmic domain, and the truncated receptor complex is terminally degraded in the lysosomes. These data establish a critical role for JAK kinases and the Ub/proteasome degradation pathway in IL-5R down-regulation.
    Journal of Leukocyte Biology 05/2007; 81(4):1137-48. · 4.30 Impact Factor
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    David P Huston
    Annals of internal medicine 10/2006; 145(6):454-8. · 16.10 Impact Factor
  • David P Huston, Yong Jun Liu
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    ABSTRACT: Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine that has recently been implicated as central to the microenvironment and is permissive for the immunologic cascade that initiates and propagates allergic immune responses. In humans, TSLP is produced predominantly by epithelial cells and activated mast cells, and stimulates myeloid dendritic cells (mDC), which uniquely express the heterodimeric TSLP receptor. TSLP-activated mDC can promote naïve CD4+ T cells to differentiate into a Th2 phenotype and can promote the expansion of CD4+ Th2 memory cells. Recent evidence implicates TSLP as playing a pivotal role in the pathobiology of allergic asthma and atopic dermatitis. The potential for TSLP to provide a new therapeutic target for the treatment of allergic disorders is compelling, and elucidating the mechanisms that regulate TSLP expression and the effects of TSLP on orchestrating the immune response toward a Th2 phenotype should facilitate this quest.
    Current Allergy and Asthma Reports 10/2006; 6(5):372-6. · 2.45 Impact Factor
  • Current Allergy and Asthma Reports 09/2006; 6(5):355-356. · 2.45 Impact Factor
  • Julie Y. Patel, David P. Huston
    Current Allergy and Asthma Reports 09/2005; 5(5):348-349. · 2.45 Impact Factor
  • Julie Y. Patel, David P. Huston
    Current Allergy and Asthma Reports 09/2005; 5(5):347-348. · 2.45 Impact Factor
  • David P. Huston, Paul J. Utz, C. Garrison Fathman
    Clinical Immunology 04/2005; 115(1):1-2. · 3.99 Impact Factor
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    ABSTRACT: To investigate the role of CXCL13 in the development and pathogenesis of collagen-induced arthritis (CIA), and to determine the mechanisms involved in the modulation of arthritogenic response by CXCL13 neutralization. Mice were immunized with type II collagen (CII) and treated with anti-CXCL13 or control antibodies during boosting. Mice were monitored for the development and severity of arthritis. The effects of CXCL13 neutralization on immune response to CII were evaluated by cytokine production by CII-specific T cells and CII-specific antibody production. Follicular response in the spleen and in synovial tissue was determined by in situ immunohistology. Mice receiving neutralizing antibodies to CXCL13 developed significantly less severe arthritis compared with mice injected with phosphate buffered saline or control antibodies. Follicular response both in the spleen and in synovial tissue was inhibited by anti-CXCL13 treatment. Injection with anti-CXCL13 antibodies did not significantly affect antigen-specific recall lymphocyte proliferation or type 1 cytokine production in vitro. Antibody response specific to CII was not inhibited by anti-CXCL13 treatment. However, anti-CXCL13 treatment induced significantly higher levels of interleukin-10 production after in vitro CII stimulation. Neutralization of CXCL13 inhibits the development of CIA and reduces follicular response in both lymphoid and nonlymphoid tissues. These findings may have important implications regarding the pathogenesis and treatment of autoimmune arthritis.
    Arthritis & Rheumatology 03/2005; 52(2):620-6. · 7.87 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2005; 115(2). · 11.25 Impact Factor
  • H. Lu, Y. Yang, D. P. Huston, X. Yang
    Journal of Allergy and Clinical Immunology 02/2005; 115(2). · 11.25 Impact Factor

Publication Stats

2k Citations
515.09 Total Impact Points


  • 2008–2012
    • Texas A&M University System Health Science Center
      • • Microbial and Molecular Pathogenesis
      • • Department of Medicine
      Bryan, TX, United States
  • 2010–2011
    • Translational Genomics Research Institute
      Phoenix, Arizona, United States
    • Cincinnati Children's Hospital Medical Center
      • Division of Allergy and Immunology
      Cincinnati, OH, United States
  • 2009
    • University of Texas Health Science Center at Houston
      Houston, Texas, United States
  • 2007
    • University of Texas MD Anderson Cancer Center
      • Department of Immunology
      Houston, TX, United States
  • 1988–2006
    • Baylor College of Medicine
      • • Department of Medicine
      • • Department of Neurology
      Houston, TX, United States
  • 2001
    • Tan Tock Seng Hospital
      Tumasik, Singapore
  • 1997
    • Houston Zoo
      Houston, Texas, United States