IL-5 acts as a pleiotropic cytokine, signaling to multiple different cell types to converge on promoting survival in acute lung injury
Active Project Grant Awarded Last action
- Award ID
- F31HL182245
- Recipient
-
Rector & Visitors Of The University Of Virginia UEI JJG6HU8PA4S5
- Awarding agency
-
National Heart Lung and Blood Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $42,749
Award facts
- Assistance listing
- 93.837 Cardiovascular Diseases Research
- Completion date 0% complete
- Place of performance
- Charlottesville, VA 22904, USA
Award details come from USAspending.gov.
Description
- Abstract
- Acute lung injury (ALI) is a common complication following trauma to the heart post-surgery, post-cardiac arrest, and can occur for many other reasons, such as lung infection or sepsis. Previous work from our lab established that ILC2-derived IL-5 promotes survival during bleomycin (BLEO)-induced ALI. IL-5 is a critical cytokine for eosinophils, and this pathway is a successful drug target of eosinophil-driven diseases such as eosinophilic asthma. While anti-IL-5 therapeutics successfully limit eosinophilic asthma symptoms in children, these children still experience asthmatic exacerbations. During BLEO-induced ALI, treatment with IL-5 not only increased survival, but also reduced red blood cells in the airway and less pulmonary edema. If IL-5 is beneficial in some contexts, but neutralizing IL-5 signaling is not entirely effective against eosinophil-driven diseases, IT is important to dissect the protective roles of IL-5 signaling are during ALI. We found that eosinophil-deficient mice had no difference in survival from BLEO-induced ALI compared to controls, suggesting an eosinophil independent role for IL-5RΑ. At homeostasis, ILC2-derived IL-5 supports B-1 cell development in body cavities and the lung. Further, my CO-sponsor, DR. Sturek has shown that the B-1 subset is recruited to the airways and lung parenchyma, where they protect against ALI, in part through natural antibody (NAB) production. However, whether IL-5 protects against ALI through the expansion and activation of B-1 cells remains unknown. Thus, my overall hypothesis is that during BLEO-induced ALI, IL-5 promote survival in acute lung injury via B-1 cells. To address this hypothesis, we have generated a novel mouse model allowing for the selective depletion of IL-5RΑ using the CRE-LOX system. The long-term goal of this study is to dissect the protective roles of B cells and IL-5 signaling during ALI. To achieve these goals, I propose the following aims. Aim 1: determine the role of IL-5RΑ+ B cells during IL-5- induced protection from ALI. I hypothesize that IL-5 signaling during ALI increases IL-5RΑ+ B cells which are protective. Aim 2: determine if IL-5 signaling influences specificity of B cell antibodies during ALI. I hypothesize that exogenous IL-5 treatment or endogenous IL-5 during ALI serves as the signal for B cells to produce more OSE-specific antibodies. Impact: this work will both unravel how IL-5 signaling protects during acute lung injury and further explore the effect IL-5 exclusively on B cells. These studies could potentially reveal a new therapeutic use for IL-5. Additionally, the techniques proposed, the experimental planning and set-up, the mentorship opportunities, and the planned manuscripts, conference presentations and networking will prepare me for a future career as an academic principal investigator.
Quick answers
Who received award F31HL182245?
F31HL182245 was awarded to Rector & Visitors Of The University Of Virginia by National Heart Lung and Blood Institute (National Institutes of Health) on February 16, 2027.
How much is award F31HL182245 worth?
$42,749 has been obligated on F31HL182245.
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