Keywords

Influenza, Immunology, Kinetics, IL-2, Therapeutic, Lungs

Abstract

Influenza A virus (IAV) causes an acute respiratory tract infection. Despite the availability of seasonal vaccines and antiviral drugs, IAV remains a global health concern. Additional therapeutic strategies to treat severe IAV infection that are effective beyond the first 48 hours of infection, when anti-viral drugs such as Tamiflu and Relenza are no longer beneficial, are urgently needed. Prior studies from our group suggest that an IL-2-based therapeutic approach directly promotes pathways to temper inflammation and improve tissue integrity, while also, concomitantly, enhancing anti-viral immunity when initiated as late as 4 days post-infection. In these studies, targeting IL-2 towards the high-affinity subunit (CD25) of the IL-2 receptor alpha (CD25) during IAV infection significantly reduced bronchial inflammation, expanded Foxp3 CD4+ T regulatory T cells, and promoted anti-viral T cell activation. Other immune as well as non-immune cells, however, have potential to express CD25. To get a better understanding of lung cells with potential to respond to IL-2 and gain insights into the underlying cellular mechanisms contributing to the beneficial outcomes observed, here we use flow cytometry to kinetically characterize CD25 expression on hematopoietic (innate and adaptive immune cells) and non-hematopoietic (endothelial and epithelial) cell populations in murine lungs following IAV infection with and without CD25-targeted IL-2 treatment. Proliferation of various cell populations in the lungs was also determined via Ki-67 expression. Our results demonstrate that CD25 is broadly and dynamically expressed on various cell types, including immune and non-hematopoietic cells. Notably, non-hematopoietic cells expressing CD25 exhibited significantly increased proliferation, as indicated by Ki-67 expression, following treatment with CD25-targeted IL-2 at timepoints that coincide with repair of virus infection-induced damage. These findings suggest that CD25-targeted IL-2 not only modulates immune responses but may also promote lung tissue repair, offering a promising late-stage therapeutic strategy to mitigate IAV-induced damage and enhance pulmonary regeneration.

Completion Date

2025

Semester

Fall

Committee Chair

Strutt, Tara

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Format

PDF

Release Date

12-15-2027

Document Type

Thesis

Campus Location

College of Medicine

Subjects

Influenza--Immunological aspects; Interleukin-2; Influenza--Treatment; Cytokines--Therapeutic use; Infection--Immunotherapy

Download

Available for download on Wednesday, December 15, 2027

Share

COinS
 

Accessibility Statement

This item was created or digitized prior to April 24, 2027, or is a reproduction of legacy media created before that date. It is preserved in its original, unmodified state specifically for research, reference, or historical recordkeeping. In accordance with the ADA Title II Final Rule, the University Libraries provides accessible versions of archival materials upon request. To request an accommodation for this item, please submit an accessibility request form.