A treatment-resistant, severe type of asthma successfully modeled in mice
The model illuminates underlying biology and immune activity of lung cells involved in neutrophilic asthma
- Date:
- February 18, 2025
- Source:
- Michigan Medicine - University of Michigan
- Summary:
- Researchers are tackling neutrophilic asthma, successfully developing one of the first mouse models of the condition.
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A better understanding of inflammation and lung immunity over the past two decades has led to new, innovative treatments for asthma, including biologic therapies.
This is especially true for a subtype known as eosinophilic asthma -- asthma that's related to the recruitment and overactivation of white blood cells in the lungs called eosinophils.
However, a different type of asthma called neutrophilic asthma has fewer treatment options and doesn't respond as well to first line asthma therapy.
As a result, people with this type of asthma, which is usually diagnosed in adults, often experience more serious disease and a poorer quality of life.
A team of researchers led by Anukul Shenoy, Ph.D., of the Department of Microbiology and Immunology and the Division of Pulmonary and Critical Care Medicine at U-M and Joseph Mizgerd, Ph.D., of Boston University Chobanian & Avedisian School of Medicine are trying to address a lack of knowledge around neutrophilic asthma and have developed one of the first mouse models for the condition.
By repeatedly, but briefly, exposing mice to an inhaled allergen over time, they were able to mimic the exposure and immune activity within the airways of adult humans.
This type of allergen exposure resulted in an increase in accumulation of different types of T cells called CD4+TRM cells -- memory cells that are present in adult lungs and responsible for a rapid response to a previously encountered allergen.
When activated, one subset of CD4+TRM cells lining the airways produces a cytokine IL-17A which then persuades the epithelial cells of the lung to recruit neutrophils, a type of white blood cell that causes inflammation.
While neutrophils are important for protection against pathogens their activation in response to a harmless allergen in asthmatics leads to severe lung damage.
Interestingly, the team also discovered that the epithelial cells try and control this inflammation by using a specialized immune-facing molecule called MHC-II.
They do so by using MHC-II to instruct a different subset of CD4+TRM cells in the airways to produce a cytokine IFN-gamma, which then potently suppressed inflammation in this mouse model of neutrophilic asthma.
Story Source:
Materials provided by Michigan Medicine - University of Michigan. Original written by Kelly Malcom. Note: Content may be edited for style and length.
Journal Reference:
- Vijay Raaj Ravi, Filiz T. Korkmaz, Carolina Lyon De Ana, Lu Lu, Feng-Zhi Shao, Christine V. Odom, Kimberly A. Barker, Aditya Ramanujan, Emma N. Niszczak, Wesley N. Goltry, Ian M.C. Martin, Catherine T. Ha, Lee J. Quinton, Matthew R. Jones, Alan Fine, Joshua D. Welch, Felicia Chen, Anna C. Belkina, Joseph P. Mizgerd, Anukul T. Shenoy. Lung CD4+ resident memory T cells use airway secretory cells to stimulate and regulate onset of allergic airway neutrophilic disease. Cell Reports, 2025; 115294 DOI: 10.1016/j.celrep.2025.115294
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