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

作者：Bsibsi Malika; Holtman Inge R; Gerritsen Wouter H; Eggen Bart J L; Boddeke Erik; van der Valk Paul; van Noort Johannes M; Amor Sandra^*

来源：Journal of Neuropathology and Experimental Neurology, 2013, 72(10): 970-979.

DOI：10.1097/NEN.0b013e3182a776bf

• Alpha-B-crystallin
• Microglia
• Multiple sclerosis
• Oligodendrocytes
• Preactive MS lesions

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 %26quot;preactive MS lesions,%26quot; 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.

• 出版日期2013-10