| Author: | Yeh, Yu-wen |
| Title: | Mouse hygiene status—a tale of two environments for mast cells |
| Degree: | Ph.D. |
| Year: | 2024 |
| Subject: | Mast cells Mice as laboratory animals Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Health Technology and Informatics |
| Pages: | xvi, 116 pages : color illustrations |
| Language: | English |
| Abstract: | Conventional laboratory mice profoundly lack lung parenchymal mast cells, a major cell type contributing to allergic inflammation, which clearly contrasts the abundant expression of these cells in human lungs. Meanwhile, accumulating experimental evidence suggests that wild mice living in a dirty environment have an immune system more closely resembling that of humans. However, prior to my research, no information was available regarding the mast cell distribution in the lung tissues of wild mice. In this thesis work, I set forth to investigate the lung distribution of mast cells in free-living wild mice and pet mice that were also kept in a less clean environment. Here, I provide compelling evidence demonstrating the presence of mast cells at a substantial density in the lung parenchymal tissues of wild mice trapped in Norway and India and pet store mice obtained from Taiwan. Consistently, wild mice expressed higher pulmonary levels of stem cell factor (SCF), a critical mast cell growth factor. Next, I was intrigued to confirm whether environmental factors could impact the distribution of lung mast cells. To this end, C57BL/6 laboratory mice were maintained in a purpose-built enclosure with bedding materials, including soil, twigs, fallen leaves, grass, and hay, obtained from a farmland environment with a wild rodent infestation, which was expected to provide a rich supply of microbial species that could “naturalize” the laboratory mice, resulting in their expanded diversity and richness of the microbiota toward a more “wild phenotype”. Their offspring were raised to adulthood in this dirty environment (neonatal exposure). Alternatively, some clean adult laboratory mice were placed in this dirty environment for the same length of time (adult exposure). Laboratory mice with neonatal exposure, but not adult exposure, to this dirty, semi-natural environment developed extensively reshaped gut microbiota composition. Interestingly, laboratory mice exposed to a dirty environment right after birth did have lung parenchymal mast cells at adulthood. In sharp contrast, adult exposure failed to allow laboratory mice to repopulate their lung mast cells. Increased lung mast cell accumulation after neonatal exposure was accompanied with augmented production of mast cell growth cytokines, including SCF, in the lung tissues. In addition, the naturalization of laboratory mice was capable of regulating pulmonary inflammation and humoral immune responses in a mouse model of asthma. The naturalization or rewilding approach designed in this thesis work offers a promising solution for developing mouse models with lung parenchymal mast cells, which are predicted to be more relevant to model human asthma—a disease strongly associated with pulmonary mast cells. |
| Rights: | All rights reserved |
| Access: | open access |
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