Respiratory conditions represent a significant global healthcare burden impacting hundreds of millions worldwide and necessitating new treatment paradigms. Pulmonary immune engineering using synthetic nanoparticle (NP) platforms can reprogram immune responses for therapeutically beneficial or protective responses directly within the lung tissue. However, effectively localizing these game-changing approaches to the lung remains a significant challenge due to the lung's natural defense. We highlight the target pulmonary immune cells and address advances to localize NPs to the lung via both aerosol and vascular delivery. For each administration route, we discuss physiochemical design rules and recent immune-modulatory successes of synthetic, extracellular vesicle, and cell-mediated NP delivery. We aim to provide readers with an updated summary of this emerging field and offer a roadmap for future research aimed at enhancing the efficacy of pulmonary immunotherapies.
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http://dx.doi.org/10.1146/annurev-chembioeng-082223-105117 | DOI Listing |
J Immunol
January 2025
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA, United States.
Macrophages are critical to maintaining and restoring tissue homeostasis during inflammation. The lipid metabolic state of macrophages influences their function and polarization, which is crucial to the resolution of inflammation. The contribution of lipid synthesis to proinflammatory macrophage responses is well understood.
View Article and Find Full Text PDFSci Transl Med
March 2025
Department of Molecular Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Interstitial lung disease (ILD) consists of a group of immune-mediated disorders that can cause inflammation and progressive fibrosis of the lungs, representing an area of unmet medical need given the lack of disease-modifying therapies and toxicities associated with current treatment options. Tissue-specific splice variants (SVs) of human aminoacyl-tRNA synthetases (aaRSs) are catalytic nulls thought to confer regulatory functions. One example from human histidyl-tRNA synthetase (HARS), termed HARS because the splicing event resulted in a protein encompassing the WHEP-TRS domain of HARS (a structurally conserved domain found in multiple aaRSs), is enriched in human lung and up-regulated by inflammatory cytokines in lung and immune cells.
View Article and Find Full Text PDFJ Immunol
February 2025
Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, United States.
Persistent systemic inflammation is associated with an elevated risk of cardiometabolic diseases. However, the characteristics of the innate and adaptive immune systems in individuals who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric and other immune phenotyping analyses, which limits our understanding of their relationship to disease states.
View Article and Find Full Text PDFAnnu Rev Chem Biomol Eng
March 2025
1Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA; email:
Respiratory conditions represent a significant global healthcare burden impacting hundreds of millions worldwide and necessitating new treatment paradigms. Pulmonary immune engineering using synthetic nanoparticle (NP) platforms can reprogram immune responses for therapeutically beneficial or protective responses directly within the lung tissue. However, effectively localizing these game-changing approaches to the lung remains a significant challenge due to the lung's natural defense.
View Article and Find Full Text PDFJ Immunol
March 2025
Department of Environmental Health, Boston University School of Public Health, Boston, MA, United States.
While immunotherapy has shown some efficacy in lung adenocarcinoma (LUAD) patients, many respond only partially or not at all. One limitation in improving outcomes is the lack of a complete understanding of immune checkpoint regulation. Here, we investigated a possible link between an environmental chemical receptor implicated in lung cancer and immune regulation, the AhR, a known but counterintuitive mediator of immunosuppression (interferon (IFN)-γ), and regulation of two immune checkpoints (PD-L1 and IDO).
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