IL-10-providing B cells govern pro-inflammatory activity of macrophages and microglia in CNS autoimmunity
Autor: | Anastasia Geladaris, Silke Häusser-Kinzel, Roxanne Pretzsch, Nitzan Nissimov, Klaus Lehmann-Horn, Darius Häusler, Martin S. Weber |
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Rok vydání: | 2023 |
Předmět: | |
Zdroj: | Acta Neuropathologica. 145:461-477 |
ISSN: | 1432-0533 0001-6322 |
Popis: | B cells contribute to chronic inflammatory conditions as source of antibody-secreting plasma cells and as antigen-presenting cells activating T cells, making anti-CD20-mediated B cell depletion a widely used therapeutic option. B cells or B cell subsets may, however, exert regulatory effects, while to date, the immunological and/or clinical impact of these observations remained unclear. We found that in multiple sclerosis (MS) patients, B cells contain regulatory features and that their removal enhanced activity of monocytes. Using a co-culture system, we identified B cell-provided interleukin (IL)-10 as key factor in controlling pro-inflammatory activity of peripheral myeloid cells as well as microglia. Depleting B cells via anti-CD20 in a mouse model of MS unleashed the activity of myeloid cells and microglia and accelerated disease severity; in contrast, adoptive transfer of IL-10-providing B cells restored in vivo control of central nervous system (CNS) macrophages and microglia and reversed clinical exacerbation. These findings suggest that B cells exert meaningful regulatory properties, which should be considered when designing novel B cell-directed agents. |
Databáze: | OpenAIRE |
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