CD22 blockade exacerbates neuroinflammation in Neuromyelitis optica spectrum disorder

Journal of Neuroinflammation, 2024 · DOI: https://doi.org/10.1186/s12974-024-03305-2 · Published: November 18, 2024

Simple Explanation

This study investigates the role of CD22, a molecule that regulates immune cell activity, in neuromyelitis optica spectrum disorder (NMOSD), an autoimmune disease affecting the central nervous system. The researchers explored how CD22 influences microglia, key immune cells in the brain, and the resulting inflammation and damage in NMOSD. The study used single-cell sequencing and flow cytometry to analyze CD22 expression in immune cells from NMOSD patients and a mouse model. They also examined how blocking CD22 affects brain lesions, inflammation, and the activity of microglia and other immune cells. The findings suggest that CD22 normally plays a protective role in NMOSD by limiting the damaging activity of microglia and other immune cells. Blocking CD22 led to increased inflammation and worsened disease outcomes in the mouse model.

Study Duration

Not specified

Participants

Human peripheral blood from NMOSD patients and controls (n = 5 per group). Mouse model of NMOSD (n = 8 per group)

Evidence Level

Not specified

Key Findings

1
CD22 is expressed in B cells, neutrophils, monocytes, and microglia-derived exosomes in human peripheral blood from NMOSD patients and controls, as well as in a mouse model of NMOSD.
2
CD22 blockade in mice increased CNS lesions, astrocyte loss, demyelination, inflammatory activity, and phagocytosis in microglia.
3
The detrimental effects of CD22 blockade were alleviated by depleting microglia or Gr-1+ myeloid cells, and diminished with a phosphorylated SYK inhibitor.

Research Summary

This study reveals CD22 as a key molecular switch governing the beneficial effects of microglia and Gr-1+ myeloid cells in NMOSD pathology. CD22 blockade exacerbated NMOSD lesions, astrocyte loss, and CNS demyelination, accompanied by increased inflammatory activity of microglia and CNS infiltration of peripheral myeloid cells. The detrimental effects of CD22 blockade in NMOSD pathology involve mainly microglia and Gr-1+ myeloid cells, but not B cells, in a process involving SYK-GSK3β signaling. These findings reveal a previously unrecognized role of CD22 in CNS inflammation and NMOSD pathology, suggesting its potential clinical implications for future immune therapies.

Practical Implications

Therapeutic Target Identification

CD22 can be explored as a potential therapeutic target for NMOSD, focusing on modulating microglia and Gr-1+ myeloid cell activity.

Drug Development

Development of CD22 agonists to reduce the activity of overactive microglia and other myeloid cells in CNS autoimmune diseases like NMOSD.

Personalized Treatment Strategies

CD22 modulation may serve as a combined therapy with current treatments for various brain diseases, tailored to specific disease contexts.

Study Limitations

1
The potential effects of CD22 blockade on B-cell activity in patients with NMOSD are inadequately understood and deserve further investigation.
2
The precise mechanisms underlying the benefit of CD22-expressing Gr1+ myeloid cells in NMOSD remain unclear.
3
The disease-specific effects of CD22 blockade on microglial activity and CNS injury are context dependent and involve specific immune mechanisms, which should be interpreted with caution.

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