A Gene-Dosage Effect for Interleukin-4 Receptor α-Chain Expression Has an Impact on Th2- Mediated Allergic Inflammation during Bronchopulmonary Mycosis

Müller, Uwe; Stenzel, Werner; Köhler, Gabriele; Polte, Tobias; Blessing, Manfred; Mann, Amrit; Piehler, Daniel; Brombacher, Frank; Alber, Gottfried
December 2008
Journal of Infectious Diseases;12/1/2008, Vol. 198 Issue 11, p1714
Academic Journal
Interleukin (IL)-4 and IL-13 are key factors in the pathogenesis of bronchopulmonary mycosis induced in mice by infection with Cryptococcus neoformans. Both cytokines use the IL-4 receptorα-chain (IL-4Rα). In this study, we investigated the role played by IL-4Rα expression in susceptibility to pulmonary C. neoformans infection. IL- 4Rα-/- mice were extremely resistant.Tocharacterize the effect of IL-4Rα expression levelondisease outcome,we generated IL-4Rα+-/- first-generation (F1) mice. IL-4Rα+-/- mice showed intermediate levels of IL-4Rα expression, in contrast to higher levels in wild-type mice and no expression in IL-4Rα-/- mice, indicating biallelic expression of the gene for IL-4Rα (Il4ra). Concomitant with intermediate IL-4Rα expression, F1 mice showed intermediate susceptibility associated with altered Th2/Th17 cytokine production, decreased immunoglobulin E levels, and reduced allergic inflammation. This indicates a gene-dosage effect of IL-4Rα expression on susceptibility to bronchopulmonary mycosis. These data provide the basis for novel therapies antagonizing IL-4Rα in Th2-related pulmonary infection and possibly also in asthma.


Related Articles

  • Intravenous immunoglobulin prevents release of proinflammatory cytokines in human monocytic cells stimulated with procalcitonin. Murakami, Kazuki; Suzuki, Chiaki; Fujii, Akihiro; Imada, Teruaki // Inflammation Research;Jun2012, Vol. 61 Issue 6, p617 

    Objective: The aim of this study was to investigate whether the stimulation of monocytic cells with procalcitonin (PCT) results in the release of proinflammatory cytokines. The effects of intravenous immunoglobulin (IVIG) on the production of cytokines from the cells stimulated with PCT were...

  • Cytokine Antagonists for the Treatment of Asthma. Antoniu, Sabina Antonela // BioDrugs;2009, Vol. 23 Issue 4, p241 

    Asthma is a disease of the airways in which several cytokines such as interleukin (IL)-4, IL-5, IL-13 and tumor necrosis factor-α (TNFα) play a major role in the development and progression of inflammation, airway hyperresponsiveness, mucus production, and airway remodeling. The...

  • Interleukin-17 regulation: an attractive therapeutic approach for asthma. Seoung Ju Park; Yong Chul Lee // Respiratory Research;2010, Vol. 11, p78 

    Interleukin (IL)-17 is recognized to play a critical role in numerous immune and inflammatory responses by regulating the expression of various inflammatory mediators, which include cytokines, chemokines, and adhesion molecules. There is growing evidence that IL-17 is involved in the...

  • The gene encoding interleukin-13: a susceptibility locus for asthma and related traits. Wills-Karp, Marsha // Respiratory Research;2000, Vol. 1, p19 

    Asthma is a complex inflammatory disorder controlled by both genetic and environmental influences. Multiple genetic analyses have identified the T helper type 2 (Th2) cytokine gene cluster on chromosome 5q as a susceptibility locus for asthma. Recently, the Th2 cytokine interleukin-13 has been...

  • Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. Flood-Page, Patrick; Menzies-Gow, Andrew; Phipps, Simon; Sun Ying; Wangoo, Arun; Ludwig, Mara S.; Barnes, Neil; Robinson, Douglas; Kay, A. Barry; Ying, Sun // Journal of Clinical Investigation;Oct2003, Vol. 112 Issue 7, p1029 

    Eosinophil-derived TGF-beta has been implicated in remodeling events in asthma. We hypothesized that reduction of bronchial mucosal eosinophils with anti-IL-5 would reduce markers of airway remodeling. Bronchial biopsies were obtained before and after three infusions of a humanized, anti-IL-5...

  • Gene of the month: Interleukin 6 (IL-6). Ataie-Kachoie, Parvin; Pourgholami, Mohammad H.; Richardson, Des R.; Morris, David L. // Journal of Clinical Pathology;Nov2014, Vol. 67 Issue 11, p932 

    The Interleukin 6 (IL-6) gene encodes the classic proinflammatory cytokine IL-6. It is also known as interferon-β2 (IFN-β2), B cell stimulatory factor-2 and hybridoma/plasmacytoma growth factor. IL-6 is a multifunctional cytokine with a central role in many physiological inflammatory and...

  • Modulating Effects of Intravenous Immunoglobulins on Serum Cytokine Levels in Patients with Primary Hypogammaglobulinemia. Ibánez, Cristina; Suñé, Pilar; Fierro, Ana; Rodríguez, Santiago; López, Maite; Álvarez, Antonio; De Gracia, Javier; Montoro, José-Bruno // BioDrugs;2005, Vol. 19 Issue 1, p59 

    Background: Intravenous immunoglobulins (IVIG) have usually been administered for replacement therapy of humoral immunodeficiencies, but their use in treating other disorders with an immune pathogenesis is increasing. The exact mechanism of action by which IVIG are of benefit in such diseases is...

  • Lentiviral-mediated GATA-3 RNAi Decreases Allergic Airway Inflammation and Hyperresponsiveness. Chen-Chen Lee; Hsin-Ying Huang; Bor-Luen Chiang // Molecular Therapy;Jan2008, Vol. 16 Issue 1, p60 

    GATA-3 is the key transcriptional factor for Th2 commitment in T cells and is strongly associated with asthma and allergic disease. We studied the silencing of the GATA-3 gene expression using RNA interference (RNAi) delivered by a lentiviral vector, to evaluate the therapeutic role of GATA-3...

  • Resistance to Cryptococcus neoformans infection in the absence of CD4 + T cells. Aguirre, Karen; Crowe, Jason; Haas, Amy; Smith, Janel // Medical Mycology;Feb2004, Vol. 42 Issue 1, p15 

    Previous studies of Cryptococcus neoformans infection have revealed a role for CD4 + T cells and CD8 + T cells in anticryptococcal resistance in the lungs, but such a role has been revealed only for CD4 + T cells in the brains of experimentally infected mice. In this study, we found that mice...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics