ASTHMA, AIRWAY INFLAMMATION AND PTSD ASSOCIATION: RELEVANT MODELS AND A ROLE OF IL17A
Psychosomatic Medicine
; 84(5):A141-A142, 2022.
Article
in English
| EMBASE | ID: covidwho-2003398
ABSTRACT
Background:
There is a growing interest in airway inflammation and mental health. Recent genetic and epidemiological evidence supports an association between PTSD and asthma however, contributory immune mediators/mechanisms are unclear. Recent work from our group employs mouse aeroallergen, house dust mite (HDM) models to examine the role of severe asthma linked inflammatory T helper cells, Th17 and interleukin 17 (IL-17A) in regulating PTSD-relevant behaviors.Methods:
A combination of behavioral, immunological, transgenic and transcriptomic approaches were used. 1) BALBc-C5a receptor treatment that shifts Th2 mild asthma phenotype to Th17/IL17a expansion and robust airway inflammation;2) IL-17a receptor knockout mice and 3) RNAseq transcriptomics of cortical and blood brain barrier compromised area, subfornical organ (SFO) tissue was performed. Fear conditioning and extinction was assessed as a PTSD-relevant behavior.Results:
Induction of Th17/IL-17 in the BALBc/anti-C5aR1 treated mice resulted in compromised fear extinction and increased fear reinstatement. Absence of IL-17 signaling in IL17Ra deficient mice attenuated HDM effects on fear extinction. Preliminary evidence suggests a potential of the SFO in translating HDM effects to the medial prefrontal cortex, an area regulating fear extinction. Transcriptomic analyses revealed modulation of immune T cell-targeted signaling pathways within the SFO in mice with Th17A expansion.Conclusion:
Overall, our work provides novel insights on mechanisms by which mediators of severe airway inflammation, Th17/IL17A regulate fear memory of relevance to PTSD. Beyond asthma-PTSD, our findings have relevant implications for other pulmonary (e.g. COVID-19) and autoimmune inflammatory conditions and mental health.
complement component C5a receptor; endogenous compound; interleukin 17; interleukin 17 receptor; animal cell; animal experiment; animal model; asthma; blood brain barrier; conference abstract; controlled study; coronavirus disease 2019; Dermatophagoides; fear; human; inflammation; knockout mouse; language; male; medial prefrontal cortex; memory; mental health; mouse; nonhuman; phenotype; posttraumatic stress disorder; protein function; respiratory tract inflammation; RNA sequencing; signal transduction; subfornical organ; T lymphocyte; transcriptomics; transgene
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Psychosomatic Medicine
Year:
2022
Document Type:
Article
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