Skip to main content

Filter Search Results

Publication Year

Animal Models

Topic Area

Methods

Funding Mechanism

Division of Comparative Medicine

Collaborating ICs

Selected Grantee Publications

Loss of Lymphatic IKKα Disrupts Lung Immune Homeostasis, Drives BALT Formation, and Protects Against Influenza

Cully et al., Immunohorizons. 2024.

https://pubmed.ncbi.nlm.nih.gov/39007717/

Tertiary lymphoid structures (TLS) have context-specific roles, and more work is needed to understand how they function in separate diseases to drive or reduce pathology. Researchers showed previously that lymph node formation is ablated in mice constitutively lacking IκB kinase alpha (IKKα) in lymphatic endothelial cells (LECs). In this study, they demonstrated that loss of IKKα in lymphatic endothelial cells leads to the formation of bronchus-associated lymphoid tissue in the lung. Additionally, they showed that male and female mice challenged with influenza A virus (IAV) exhibited markedly improved survival rates and reduced weight loss, compared with littermate controls. They concluded that ablating IKKα in this tissue reduces the susceptibility of the mice to IAV infection through a decrease in proinflammatory stimuli. This work provides a new model to explore the mechanisms of TLS formation and the immunoregulatory function of lung lymphatics. Supported by ORIP (T35OD010919), NHLBI, NIAID, and NIAMS.

PGRN Deficiency Exacerbates, Whereas a Brain Penetrant PGRN Derivative Protects, GBA1 Mutation–Associated Pathologies and Diseases

Zhao et al., Proc Natl Acad Sci USA. 2023.

https://www.pnas.org/doi/10.1073/pnas.2210442120

Mutations in GBA1 are associated with Gaucher disease (GD) and are also genetic risks in developing Parkinson’s disease (PD). Investigators created a mouse model and demonstrated that progranulin (PGRN) deficiency in Gba1 mutant mice caused early onset and exacerbated GD phenotypes, leading to substantial increases in substrate accumulation and inflammation in visceral organs and the central nervous system. These in vivo and ex vivo data demonstrated that PGRN plays a crucial role in the initiation and progression. In addition, the mouse model provides a clinically relevant system for testing therapeutic approaches for GD and PD. Supported by ORIP (R21OD033660), NIAMS, and NINDS.