Publications by authors named "Dylan H Goldman"

2 Publications

  • Page 1 of 1

Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.

J Exp Med 2018 06 11;215(6):1627-1647. Epub 2018 Apr 11.

Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA

Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMφs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMφs to populate the niche and that the presence of beMφs does not alter behavior. Furthermore, beMφs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMφs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMφs may be possible with irradiation-free conditioning regimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1084/jem.20180247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987928PMC
June 2018

Endoplasmic reticulum stress mediates house dust mite-induced airway epithelial apoptosis and fibrosis.

Respir Res 2013 Dec 24;14:141. Epub 2013 Dec 24.

Department of Pathology, Vermont Lung Center University of Vermont College of Medicine, Burlington, VT 05405, USA.

Background: The endoplasmic reticulum (ER) stress response participates in many chronic inflammatory and autoimmune diseases. In the current study, we sought to examine the contribution of ER stress transducers in the pathogenesis of three principal facets of allergic asthma: inflammation, airway fibrosis, and airways hyperresponsiveness.

Methods: House Dust Mite (HDM) was used as an allergen for in vitro and in vivo challenge of primary human and murine airway epithelial cells. ER stress transducers were modulated using specific small interfering RNAs (siRNAs) in vivo. Inflammation, airway remodeling, and hyperresponsiveness were measured by total bronchoalveolar lavage (BAL) cell counts, determination of collagen, and methacholine responsiveness in mice, respectively.

Results: Challenge of human bronchiolar and nasal epithelial cells with HDM extract induced the ER stress transducer, activating transcription factor 6 α (ATF6α) as well as protein disulfide isomerase, ERp57, in association with activation of caspase-3. SiRNA-mediated knockdown of ATF6α and ERp57 during HDM administration in mice resulted in a decrease in components of HDM-induced ER stress, disulfide mediated oligomerization of Bak, and activation of caspase-3. Furthermore, siRNA-mediated knockdown of ATF6α and ERp57 led to decreased inflammation, airway hyperresponsiveness and airway fibrosis.

Conclusion: Collectively, our work indicates that HDM induces ER stress in airway epithelial cells and that ATF6α and ERp57 play a significant role in the development of cardinal features of allergic airways disease. Inhibition of ER stress responses may provide a potential therapeutic avenue in chronic asthma and sub-epithelial fibrosis associated with loss of lung function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1465-9921-14-141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877992PMC
December 2013