Publication

Alpha-B-Crystallin Induces an Immune-Regulatory and Antiviral Microglial Response in Preactive Multiple Sclerosis Lesions

Bsibsi, M., Holtman, I. R., Gerritsen, W. H., Eggen, B. J. L., Boddeke, E., van der Valk, P., van Noort, J. M. & Amor, S., Oct-2013, In : Journal of neuropathology and experimental neurology. 72, 10, p. 970-979 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

Microglial nodules are frequently observed in the normal-appearing white matter of multiple sclerosis (MS) patients. Previously, we have shown that these clusters, which we call "preactive MS lesions," are closely associated with stressed oligodendrocytes and myelin sheaths that contain markedly elevated levels of the small stress protein alpha-B-crystallin (HspB5). Here, we show that microglia in these lesions express the recently identified receptors for HspB5, that is, CD14, Toll-like receptor family 1 and 2 (TLR1 and TLR2), and several molecular markers of the microglial response to HspB5. These markers were identified by genome-wide transcript profiling of 12 primary human microglial cultures at 2 time points after exposure to HspB5. These data indicate that HspB5 activates production by microglia of an array of chemokines, immuneregulatory mediators, and a striking number of antiviral genes that are generally inducible by type I interferons. Together, our data suggest that preactive MS lesions are at least in part driven by HspB5 derived from stressed oligodendrocytes and may reflect a local attempt to restore tissue homeostasis.

Original languageEnglish
Pages (from-to)970-979
Number of pages10
JournalJournal of neuropathology and experimental neurology
Volume72
Issue number10
Publication statusPublished - Oct-2013

    Keywords

  • Alpha-B-crystallin, Microglia, Multiple sclerosis, Oligodendrocytes, Preactive MS lesions, APPEARING WHITE-MATTER, NF-KAPPA-B, MICROARRAY DATA, DOUBLE-BLIND, CELLS, ACTIVATION, PROTEIN, NEUROINFLAMMATION, IDENTIFICATION, INFLAMMATION

View graph of relations

ID: 13656449