TY - JOUR
T1 - Profiling of microglia nodules in multiple sclerosis reveals propensity for lesion formation
AU - van den Bosch, Aletta M R
AU - van der Poel, Marlijn
AU - Fransen, Nina L
AU - Vincenten, Maria C J
AU - Bobeldijk, Anneleen M
AU - Jongejan, Aldo
AU - Engelenburg, Hendrik J
AU - Moerland, Perry D
AU - Smolders, Joost
AU - Huitinga, Inge
AU - Hamann, Jörg
N1 - © 2024. The Author(s).
PY - 2024/2/23
Y1 - 2024/2/23
N2 - Microglia nodules (HLA-DR+ cell clusters) are associated with brain pathology. In this post-mortem study, we investigated whether they represent the first stage of multiple sclerosis (MS) lesion formation. We show that microglia nodules are associated with more severe MS pathology. Compared to microglia nodules in stroke, those in MS show enhanced expression of genes previously found upregulated in MS lesions. Furthermore, genes associated with lipid metabolism, presence of T and B cells, production of immunoglobulins and cytokines, activation of the complement cascade, and metabolic stress are upregulated in microglia nodules in MS. Compared to stroke, they more frequently phagocytose oxidized phospholipids and possess a more tubular mitochondrial network. Strikingly, in MS, some microglia nodules encapsulate partially demyelinated axons. Taken together, we propose that activation of microglia nodules in MS by cytokines and immunoglobulins, together with phagocytosis of oxidized phospholipids, may lead to a microglia phenotype prone to MS lesion formation.
AB - Microglia nodules (HLA-DR+ cell clusters) are associated with brain pathology. In this post-mortem study, we investigated whether they represent the first stage of multiple sclerosis (MS) lesion formation. We show that microglia nodules are associated with more severe MS pathology. Compared to microglia nodules in stroke, those in MS show enhanced expression of genes previously found upregulated in MS lesions. Furthermore, genes associated with lipid metabolism, presence of T and B cells, production of immunoglobulins and cytokines, activation of the complement cascade, and metabolic stress are upregulated in microglia nodules in MS. Compared to stroke, they more frequently phagocytose oxidized phospholipids and possess a more tubular mitochondrial network. Strikingly, in MS, some microglia nodules encapsulate partially demyelinated axons. Taken together, we propose that activation of microglia nodules in MS by cytokines and immunoglobulins, together with phagocytosis of oxidized phospholipids, may lead to a microglia phenotype prone to MS lesion formation.
KW - Humans
KW - Multiple Sclerosis/pathology
KW - Microglia/metabolism
KW - Nervous System Diseases/pathology
KW - Stroke/pathology
KW - Cytokines/metabolism
KW - Immunoglobulins/metabolism
U2 - 10.1038/s41467-024-46068-3
DO - 10.1038/s41467-024-46068-3
M3 - Article
C2 - 38396116
SN - 2041-1723
VL - 15
SP - 1667
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -