This item is under embargo and not available online per the author's request. For access information, please visit http://libanswers.wustl.edu/faq/5640.

Date of Award

Spring 5-15-2019

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Immunology)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Chronic obstructive lung disease (COPD) causes substantial human and economic costs both in the US and worldwide. To identify the molecular mechanisms to allow for targeted therapies for COPD, we developed a high-fidelity mouse model of chronic lung inflammation using the natural rodent pathogen Sendai virus (SeV). While nucleic acid-sensing pattern recognition receptors are important for innate immune responses to viral pathogens, there have been few studies investigating their role in the context of chronic disease. Here we show that Toll-like receptor 3 (Tlr3) signaling is required for the development of chronic lung disease in a postviral mouse model. Activation of Tlr3 in inflammatory monocyte-derived dendritic cells (moDCs) is necessary for the development of chronic lung disease. moDCs form an immune cell niche that drives epithelial alveolar type II cell (AT2) proliferation and interleukin-33 (Il33) expression. Il33 then leads to activation of downstream effector immune cells that produce a chronic inflammatory disease phenotype.

Language

English (en)

Chair and Committee

Michael J. Holtzman

Committee Members

Gaya Amarasinghe, John P. Atkinson, Mark J. Miller, Rodney D. Newberry,

Comments

Permanent URL: https://doi.org/10.7936/yddd-qg70

Available for download on Thursday, April 23, 2020

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