We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Single-cell profiling indicates a high similarity between immune cells in the cerebrospinal fluid and in meningeal ectopic lymphoid tissue in experimental autoimmune encephalomyelitis.
- Authors
Georgieva, Tanya; Diddens, Jolien; Friedrich, Verena; Lepennetier, Gildas; Brand, Rosa Margareta; Lehmann-Horn, Klaus
- Abstract
Background and objectives: B cell depleting anti-CD20 monoclonal antibodies (aCD20 mAbs) are highly effective in treatment of multiple sclerosis (MS) but fail to halt the formation of meningeal ectopic lymphoid tissue (mELT) in the murine model experimental autoimmune encephalomyelitis (EAE). While mELT can be examined in EAE, it is not accessible in vivo in MS patients. Our key objectives were to compare the immune cells in cerebrospinal fluid (CSF), which is accessible in patients, with those in mELT, and to study the effects of aCD20 mAbs on CSF and mELT in EAE. Methods: Applying single cell RNA sequencing, we compared gene expression profiles in immune cells from (1) CSF with mELT and (2) aCD20 mAbs treated with control treated mice in a spontaneous 2D2xTh EAE model. Results: The immune cell composition in CSF and mELT was very similar. Gene expression profiles and pathway enrichment analysis revealed no striking differences between the two compartments. aCD20 mAbs led not only to a virtually complete depletion of B cells in the CSF but also to a reduction of naïve CD4 T cells and marked increase of macrophages. No remarkable differences in regulated genes or pathways were observed. Discussion: Our results suggest that immune cells in the CSF may serve as a surrogate for mELT in EAE. Future studies are required to confirm this in MS patients. The observed increase of macrophages in B cell depleted CSF is a novel finding and requires verification in CSF of aCD20 mAbs treated MS patients. Due to unresolved technical challenges, we were unable to study the effects of aCD20 mAbs on mELT. This should be addressed in future studies.
- Subjects
LYMPHOID tissue; ECTOPIC tissue; CEREBROSPINAL fluid; ENCEPHALOMYELITIS; GENE expression profiling
- Publication
Frontiers in Immunology, 2024, p1
- ISSN
1664-3224
- Publication type
Academic Journal
- DOI
10.3389/fimmu.2024.1400641