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Updated: Nov 1, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
CD22 Blockage Restores Age-Related Impairments of Microglia Surveillance Capacity
Vanessa Aires1,2,3, Claire Coulon-Bainier1, Anto Pavlovic1
1Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Abstract:
Microglia, the innate immune cells of the brain, are essential for maintaining homeostasis by their ramified, highly motile processes and for orchestrating the immune response to pathological stimuli. They are implicated in several neurodegenerative diseases like Alzheimer's and Parkinson's disease. One commonality of these diseases is their strong correlation with aging as the highest risk factor and studying age-related alterations in microglia physiology and associated signaling mechanism is indispensable for a better understanding of age-related pathomechanisms. CD22 has been identified as a modifier of microglia phagocytosis in a recent study, but not much is known about the function of CD22 in microglia. Here we show that CD22 surface levels are upregulated in aged versus adult microglia. Furthermore, in the amyloid mouse model PS2APP, Aβ-containing microglia also exhibit increased CD22 signal. To assess the impact of CD22 blockage on microglia morphology and dynamics, we have established a protocol to image microglia process motility in acutely prepared brain slices from CX3CR1-GFP reporter mice. We observed a significant reduction of microglial ramification and surveillance capacity in brain slices from aged versus adult mice. The age-related decrease in surveillance can be restored by antibody-mediated CD22 blockage in aged mice, whereas surveillance in adult mice is not affected by CD22 inhibition. Moreover to complement the results obtained in mice, we show that human iPSC-derived macrophages exhibit an increased phagocytic capacity upon CD22 blockage. Downstream analysis of antibody-mediated CD22 inhibition revealed an influence on BMP and TGFβ associated gene networks. Our results demonstrate CD22 as a broad age-associated modulator of microglia functionality with potential implications for neurodegenerative disorders.
Insights
Blocking CD22 protein restores brain immune cell function in aging. This finding is crucial for understanding and potentially treating age-related neurodegenerative diseases like Alzheimer's and Parkinson's.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are brain immune cells vital for homeostasis and disease response.
- Aging significantly impacts microglia function and is a risk factor for neurodegenerative diseases.
- CD22's role in microglia, particularly in aging, is largely unknown.
Purpose of the Study:
- Investigate the function of CD22 in aged microglia.
- Determine the effect of CD22 blockage on microglia morphology and motility.
- Explore CD22's potential as a therapeutic target for age-related neurodegeneration.
Main Methods:
- Quantified CD22 surface levels in aged vs. adult microglia.
- Assessed microglia process motility in brain slices using CX3CR1-GFP mice.
- Utilized antibody-mediated CD22 blockage in aged mice and human iPSC-derived macrophages.
- Analyzed downstream gene expression changes (BMP, TGFβ networks).
Main Results:
- CD22 surface levels increase with age and in amyloid pathology.
- Aged microglia show reduced ramification and surveillance capacity.
- CD22 blockage restored aged microglia surveillance but not in adult mice.
- CD22 inhibition enhanced phagocytic capacity in human macrophages.
Conclusions:
- CD22 is an age-associated regulator of microglia function.
- Targeting CD22 may offer therapeutic benefits for neurodegenerative disorders.
- CD22 influences BMP and TGFβ signaling pathways in microglia.
