CD2 regulates pathogenesis of asthma induced by house dust mite extract
The inflammatory immune response that is characteristic of allergic asthma is triggered by exposure to allergens such as house dust mice extract (HDME) and is driven by CD4+Th2 lymphocytes that secrete large quantities of Th2 cytokines including interleukin (IL)-4, IL-13, and IL-5. Surface expression of CD2 and its ligand CD58, is increased on the monocytes and eosinophils of asthma patients, which correlate with elevated serum IgE levels, suggesting that CD2 may contribute to allergic airway inflammation. Using a murine model of asthma, we observed that HDME-exposed Balb/c mice have increased airway hyper responsiveness (AHR), cellular infiltration, goblet cell hyperplasia, and elevated levels of Th2 cytokines in the lungs, as well as increased serum IgE levels as compared to the control mice. In contrast, AHR, and cellular infiltration were significantly reduced in HDME-exposed Cd2-/- mice. Interestingly, Il13 but not Il4 or Il5 gene expression in the lungs was significantly reduced in HDME-exposed Cd2-/- mice. Of note, the gene expression of polymeric mucins, Muc5b and Muc5ac were significantly reduced in the lungs of HDME-exposed Cd2-/- mice. Furthermore, gene expression of various protective micro RNAs were increased in the lungs of HDME-exposed Cd2-/- mice. Lastly, in a mouse model of neutrophilic asthma, Cd2-/- mice exhibit significantly reduced AHR and Il13 and Il17a gene expression. Given the established role of IL-13 in promoting goblet cell hyperplasia and mucus production during allergic asthma, and various micro RNAs regulating different aspects of asthma symptoms, our studies reveal a unique role for CD2 in both Th2-high and Th2-low asthma.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- Attribution 4.0 International
- Material Type
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Theses
- Authors
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Hashem, Tanwir
- Thesis Advisors
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Das, Rupali
- Committee Members
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Subramanian, Hariharan
Ewart, Susan
- Date
- 2019
- Program of Study
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Physiology - Master of Science
- Degree Level
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Masters
- Language
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English
- Pages
- xvii, 128 pages
- ISBN
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9781392798348
1392798345
- Permalink
- https://doi.org/doi:10.25335/r37k-wd96