Role of Sleep Disruption on Development and Recovery from Lung Injury
Abstract
Our proposed research addresses the FY20 PRMRP Topic Areas: “Sleep Disorders and Restriction” and “Respiratory Health.” Although viewed as a passive condition, sleep is a highly active and dynamic process. Convincing arguments for the fundamental need for healthy sleep comes from a vast literature on the debilitating effects of poor sleep quality and sleep loss. Experimental sleep deprivation leads to decrements in cognition, mood, and performance. Impairments in sleep quality and ensuing sleep loss dampen growth hormone secretion and impair immune function. In contrast, increased sleep is associated with improved outcomes after microbial challenge in rabbits. All of these data suggest impairments in sleep quality and quantity lead to ensuing immune dysregulation and could sensitize to the development of pneumonia or affect the severity of critical illness. Regulatory T cells function as a critical regulator of the immune system. Despite numerous publications demonstrating the effects of sleep disruption on immune dysregulation, a clear connection between sleep and Regulatory T cells function is lacking. Furthermore, while different stages of sleep are known to be important in memory consolidation where slow-wave sleep (SWS) is important for declarative memory and rapid eye movement (REM) sleep for procedural memory, there is no such data on relative importance of different sleep stages on immune function. Using a robust mouse model of sleep fragmentation in conjunction with an established pneumonia model of live Streptococcus pneumoniae, we will test the hypothesis that sleep fragmentation induces regulatory T cell dysfunction, ultimately leading to greater susceptibility and delayed recovery from pneumonia-induced lung injury.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110020
Entities
People
- Mahendra Damarla
Organizations
- Johns Hopkins University
- United States Army