Littringer, Eva, Yahia, Yousra and Sarah, Sarah Zellnitz-Neugebauer (2025) A novel, innovative Approach targeting Inflammatory Lung Diseases – Regulatory T-cell Delivery to the Lungs. Drug Delivery to the Lungs conference proceedings, 36. pp. 348-351.

Abstract

Chronic lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis are major causes of morbidity and mortality worldwide. These conditions are marked by persistent, dysregulated inflammation, often driven by imbalances in the T-cell compartment. Regulatory T cells (Tregs) play a central role in maintaining immune homeostasis and have emerged as a promising therapeutic strategy. However, systemic delivery of Tregs is limited by poor tissue targeting and off-target effects. Local delivery to the lungs, especially via inhalation, may overcome these barriers—but presents technical challenges due to the large size (5–12 μm) and fragility of Tregs during aerosolization. This study aims to establish a proof of concept that Treg size can be reduced through osmotic conditioning for effective respiratory delivery. CD4⁺ T cells were isolated from human blood and incubated in hyperosmotic NaCl solutions (600–1400 mOsm). Cell size decreased significantly without major loss of viability, as shown by flow cytometry and calcein staining. Nebulization using a mesh-based Aeroneb® device demonstrated that osmotically conditioned T cells could survive aerosolization and remain functionally responsive, as evidenced by post-nebulization viability and proliferation upon activation. We showed that osmotic preconditioning is a viable strategy to shrink T cells for aerosol delivery while preserving their viability and function. This work provides a foundational step toward the development of inhalable, cell-based immunotherapies for chronic inflammatory lung diseases.

Item Type:	Article
Keywords:	Regulatory T cells, Tregs, local delivery, inhalation
Date Deposited:	10 Mar 2026 00:45
Last Modified:	10 Mar 2026 00:45
URI:	https://oak.novartis.com/id/eprint/60010