Type 2 innate lymphoid cells (ILC2s) have recently been identified in human nasal polyps, but whether numbers of ILC2s differ by polyp endotype or are influenced by corticosteroid use is unknown. Here, we show that eosinophilic nasal polyps contained double the number of ILC2s vs. non-eosinophilic polyps. Polyp ILC2s were also reduced by 50% in patients treated with systemic corticosteroids. Further, using a fungal allergen challenge mouse model, we detected greatly reduced Th2 cytokine-producing and Ki-67+ proliferating lung ILC2s in mice receiving dexamethasone. Finally, ILC2 Annexin V staining revealed extensive apoptosis after corticosteroid treatment in vivo and in vitro. Thus, ILC2s are elevated in the eosinophilic nasal polyp endotype and systemic corticosteroid treatment correlated with reduced polyp ILC2s. Finally, allergen-challenged mice showed reduced ILC2s and increased ILC2 apoptosis after corticosteroid treatment suggesting that ILC2 may be responsive to corticosteroids in eosinophilic respiratory disease.
We believe this to be the first demonstration of myelin loss in MCI, Alzheimer's disease, and vascular dementia using a method that provides a quantitative magnetic resonance imaging-based measure of myelin. Our findings add to the emerging evidence that myelination may represent an important biomarker for the pathology of MCI and dementia. This study supports the investigation of the role of myelination in MCI and dementia through use of this quantitative magnetic resonance imaging approach in clinical studies of disease progression, and relationship of functional status to myelination status. Furthermore, mapping MWF may permit myelin to serve as a therapeutic target in clinical trials.
The relationship between regional brain myelination and aging has been the subject of intense study, with magnetic resonance imaging (MRI) perhaps the most effective modality for elucidating this. However, most of these studies have used nonspecific methods to probe myelin content, including diffusion tensor imaging, magnetization transfer ratio, and relaxation times. In the current study, we used the BMC-mcDESPOT analysis, a direct and specific method for imaging of myelin water fraction (MWF), a surrogate of myelin content. We investigated age-related differences in MWF in several brain regions in a large cohort of cognitively unimpaired participants, spanning a wide age range. Our results indicate a quadratic, inverted U-shape, relationship between MWF and age in all brain regions investigated, suggesting that myelination continues until middle age followed by decreases at older ages. We also observed that these agerelated differences vary across different brain regions, as expected. Our results provide evidence for nonlinear associations between age and myelin in a large sample of well characterized adults, using a direct myelin content imaging method.
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