Asset Details
Do you wish to reserve the book?
Characterization of Immune Response in Corticosteroid-refractory Severe Asthma in Humans and Mice
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Characterization of Immune Response in Corticosteroid-refractory Severe Asthma in Humans and Mice
Do you wish to request the book?
Characterization of Immune Response in Corticosteroid-refractory Severe Asthma in Humans and Mice
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Dissertation
Characterization of Immune Response in Corticosteroid-refractory Severe Asthma in Humans and Mice
2015
Overview
Severe asthma (SA) remains a poorly controlled disease despite use of high doses of systemic corticosteroids (CS) although mild-moderate asthma (MMA) is responsive to low dose inhaled CS. This suggests that SA cannot be solely orchestrated by Th2 cells, which are dominant in milder disease. Analysis of broncholalveolar lavage cells isolated from MMA and SA patients revealed a significantly greater IFN-γ (Th1) immune response in the airways of severe asthmatics with lower Th2 and IL-17 responses. We modeled this complex immune response seen in human SA in mice including poor response to CS. Ifng-/- mice subjected to this SA model failed to mount airway hyperresponsiveness (AHR) without appreciable effect on airway inflammation. However, Il17ra-/- mice did not show any reduction in AHR although the mice displayed lower airway inflammation. Computer-assisted pathway analysis tools linked IFN-γ to secretory leukocyte protease inhibitor (SLPI), which is expressed by airway epithelial cells and an inverse correlation between IFN-γ and SLPI expression was detected in SA. Forced expression of SLPI in mice subjected to the SA model decreased AHR in the absence of CS, and it was further reduced when SLPI was combined with CS. Taken together, our study has identified a distinct immune response in SA highlighting a dysregulated IFN-γ-SLPI axis that impacts lung function.
