Extracellular Matrix Protein Mindin is Required for the Complete Allergic Response to Fungal-Associated Proteinase.
Date
2011-09
Journal Title
Journal ISSN
Volume Title
Citation Stats
Attention Stats
Abstract
Asthma remains an important cause of morbidity and mortality with an incidence that continues to rise. Despite the importance of this disease, the mechanisms by which the host develops allergic airways disease remain poorly understood. The development of allergic airways disease appears to be contingent on activation of both the innate and adaptive immune system, but little is known about the cross-talk between these two systems. The extracellular matrix protein mindin (Spondin 2) has been previously demonstrated to have functional roles in both the innate and adaptive immunological responses. Previous work supports that pulmonary challenge with fungal-associated allergenic proteinase (FAP) induces an innate allergic response. We hypothesized that mindin would modify the biological response to FAP. Saline or FAP was administered by oropharyngeal aspiration to C57BL/6 wild type or mindin-null mice every 4 days for a total of five exposures. FAP exposed C57BL/6 mice developed enhanced airway hyperresponsiveness (AHR) to methacholine challenge and increased neutrophils and eosinophils in the bronchoalveolar lavage as compared to saline exposed controls. These responses were significantly reduced in mindin-null mice exposed to FAP. FAP challenge was associated with a broad induction of cytokines (IL-1β, TNFα, Th1, Th2, and IL-17), chemokines, and growth factors, which were reduced in mindin-null mice exposed to FAP. RNA expression in lung monocytes for representative M1 and M2 activation markers were increased by FAP, but were independent of mindin. Our observations support that challenge with FAP results in activation of both innate and adaptive immune signaling pathways in a manner partially dependent on mindin. These findings suggest a potential role for the extracellular matrix protein mindin in cross-talk between the innate and adaptive immune systems.
Type
Department
Description
Provenance
Subjects
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Tighe, Robert M, Erin N Potts, Feifei Feng, Zhuowei Li, Benjamin Frush, You-Wen He, David B Corry, Paul W Noble, et al. (2011). Extracellular Matrix Protein Mindin is Required for the Complete Allergic Response to Fungal-Associated Proteinase. Journal of allergy & therapy, 2011(Suppl 1). p. 001. 10.4172/2155-6121.s1-001 Retrieved from https://hdl.handle.net/10161/34821.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
Robert Matthew Tighe
The research focus of the Tighe laboratory is performing pulmonary basic-translational studies to define mechanisms of susceptibility to lung injury and disease. There are three principal focus areas. These include: 1) Identifying susceptibility factors and candidate pathways relevant to host biological responses to environmental pollutants such as ozone, woodsmoke and silica, 2) Defining protective and detrimental functions of lung macrophage subsets and their cross talk with the epithelium to regulate lung injury and repair, and 3) Determining the prognostic and theragnostic efficacy of 3D lung gas exchange imaging in pulmonary fibrosis using hyperpolarized 129Xenon MRI.
-
Susceptibility Factors for Environmental Lung Disease: In NIH funded studies the Tighe lab has been performing fully translational studies of lung responses to ozone. These include cell, rodent and human exposure studies to define mechanisms of susceptibility to exposure. By carefully dissecting these links, we will gain insight into how environmental pollutants acutely induce respiratory symptoms and exacerbate chronic lung diseases. This can lead to targeted therapeutics and/or identify susceptible populations. This includes exploration of genetic factors and also other metabolic and immunologic factors.
-
Pulmonary Macrophage Functions and Crosstalk with Lung Epithelial Cells: The central hypothesis of this line of research is that macrophages are key regulators of the biologic responses to environmental pollutants and the development of chronic lung disease. The Tighe laboratory has pioneered the identification of novel pulmonary macrophage subsets and has defined their function in lung injury and repair. In both published work and areas of active investigation, the Tighe lab has identified macrophage subsets with unique genetic programming and function after challenges with environmental exposures such as ozone, wood smoke and silica. Since macrophages have both detrimental and protective functions, identifying these subsets offers the opportunity to understand their unique programing and function. This could allow development of targeted therapeutics that take advantage of these functions, polarize the immune responses and alleviate respiratory disease. In addition, we are focused on macrophage and epithelial crosstalk and how their combined responses regulate lung injury and repair. These studies include omics approaches with single-cell RNA sequencing, proteomics and metabolomics and lung organoids to identify unique signals between macrophages and epithelial cells.
-
Using Hyperpolarized 129Xenon MRI to Define Prognosis and Therapy Responses in Pulmonary Fibrosis: In industry funded studies, the Tighe lab is focused on using a novel image modality to assess prognosis and therapeutic responses in individuals with pulmonary fibrosis. Pulmonary fibrosis is a disorder of progressive scar formation in the lung that causes increased shortness of breath and persistent coughing, frequently leading to death from respiratory failure. Presently, there are limited modalities that can assess prognosis in pulmonary fibrosis and can determine which individuals are responding to therapies. To address this, the Tighe lab, in collaboration with Dr. Bastiaan Driehuys in the Department of Radiology, is using inhaled hyperpolarized 129Xenon gas MRI to define regional differences in lung gas exchange in individuals with pulmonary fibrosis. Our preliminary data suggest that baseline characteristics of 129Xenon MRI associate with pulmonary fibrosis prognosis. In addition, we observe changes in the 129Xenon MRI metrics following initiation of pulmonary fibrosis therapies. These initial observations are being confirmed in ongoing clinical trials.
Benjamin Wade Frush
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.