Deciphering the Effects of Allergic Sensitization On Hematopoietic Stem and Progenitor Cells
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Authors
Stefan, Gabriella
Date
2024-10-07
Type
thesis
Language
eng
Keyword
Asthma , Hematopoietic stem cells , Innate immunity , Trained Immunity
Alternative Title
Abstract
Asthma is one of the most prevalent allergic diseases. Despite its devastating impacts on life quality and the medical system, to date, only symptomatic treatments are available. To develop novel therapeutic approaches, a better understanding of the pathomechanisms in asthma is urgently required.
Asthma is characterized by abundant infiltration of immune cells into the lungs in response to allergen exposure, as well as airway smooth muscle hypertrophy. We and others have recently demonstrated that the precursors of these innate immune cells, the hematopoietic stem and progenitor cells (HSPC) in the bone marrow (BM), can be epigenetically reprogrammed and long-term modify the host immune response in both beneficial and maladaptive ways. We thus hypothesize that respiratory allergen exposure induces functional reprogramming in hematopoietic stem cells that leads to decreased host defense capacities in deriving innate immune cells.
To investigate this hypothesis, C57BL/6J mice were sensitized with house dust mite extract and the lungs and BM were in-depth immunophenotyped by flow cytometry. We further analyzed functional capacities of HSPC-deriving innate immune cells in response to both allergic and infectious stimulation.
Interestingly, we found that asthma induction induced proliferation of HSPCs in the lung and decreased cytokine responses from bone marrow-derived macrophages to infectious stimulation.
Together, these results suggest that immunophenotypes in asthma are driven by both quantitative and qualitative changes in BM and lung HSPCs.