Protein Kinase D1 in Myeloid Cells Promotes Disease Progression and Severity in S. rectivirgula Induced Hypersensitivity Pneumonitis
type: CreativeWork
description: Introduction: Hypersensitivity pneumonitis (HP) is an inflammation driven interstitial lung disease characterized by inflammation of the interstitium, bronchioles, and alveoli of the lung that leads to granuloma formation. Myeloid lineage immune cells play a critical role in the early and late stages of the disease, and this activity is mediated through toll-like receptors (TLRs) expressed by these cells. Protein kinase D1 (PKD1) has previously been identified as a critical signaling molecule in the TLR signaling pathways of all TLR family members except for TLR3. Our previous research found that activation of protein kinase D1 (PKD1) in the lungs following exposures to Saccharopolyspora rectivirgula, a common antigen trigger for HP, contributes to acute pulmonary inflammation, IL-17A expression in the lungs, and development of HP. The purpose of our research is to elucidate the impact of PKD1 activation in myeloid cells on the onset, progression, and severity of S. rectivirgula induced HP. The method Methods: WT mice and mice in which PKD1 is knocked out in myeloid cells (the PKD1mKO group) were exposed intranasally to S. rectivirgula over short (2 hr, 6 hr, 24 hr) or extended periods of time (3-15 weeks). Disease onset and severity was analyzed by measuring mRNA expression and protein levels of inflammatory cytokines and chemokines in the lung using quantitative real-time PCR and enzyme-linked immunosorbent assays respectively. Flow cytometry was used to assess populations of different immune cells as well as surface marker expression. Masson’s Trichrome staining and hematoxylin and eosin staining was performed on tissue sections from the lung to assess alveolitis, granuloma formation, and fibrosis. Results: Compared to PKD1-sufficient WT controls, PKD1mKO animals displayed a more suppressed immune response, with lower levels of cytokines such as IL-6, IL-17A, TNFα, and IFNγ. Chemokine levels of CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL10 were also lowered. Neutrop…
abstract: Introduction: Hypersensitivity pneumonitis (HP) is an inflammation driven interstitial lung disease characterized by inflammation of the interstitium, bronchioles, and alveoli of the lung that leads to granuloma formation. Myeloid lineage immune cells play a critical role in the early and late stages of the disease, and this activity is mediated through toll-like receptors (TLRs) expressed by these cells. Protein kinase D1 (PKD1) has previously been identified as a critical signaling molecule in the TLR signaling pathways of all TLR family members except for TLR3. Our previous research found that activation of protein kinase D1 (PKD1) in the lungs following exposures to Saccharopolyspora rectivirgula, a common antigen trigger for HP, contributes to acute pulmonary inflammation, IL-17A expression in the lungs, and development of HP. The purpose of our research is to elucidate the impact of PKD1 activation in myeloid cells on the onset, progression, and severity of S. rectivirgula induced HP. The method Methods: WT mice and mice in which PKD1 is knocked out in myeloid cells (the PKD1mKO group) were exposed intranasally to S. rectivirgula over short (2 hr, 6 hr, 24 hr) or extended periods of time (3-15 weeks). Disease onset and severity was analyzed by measuring mRNA expression and protein levels of inflammatory cytokines and chemokines in the lung using quantitative real-time PCR and enzyme-linked immunosorbent assays respectively. Flow cytometry was used to assess populations of different immune cells as well as surface marker expression. Masson’s Trichrome staining and hematoxylin and eosin staining was performed on tissue sections from the lung to assess alveolitis, granuloma formation, and fibrosis. Results: Compared to PKD1-sufficient WT controls, PKD1mKO animals displayed a more suppressed immune response, with lower levels of cytokines such as IL-6, IL-17A, TNFα, and IFNγ. Chemokine levels of CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL10 were also lowered. Neutrop…
author: Snyder, John David
keywords: Hypersensitivity, Myeloid, PKD1, Pneumonitis
date published: 2025-01-01T08:00:00Z
date modified: 2026-07-24T05:00:53Z
provider: University of Tennessee Health Science Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Tennessee Health Science Center