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Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis.

Abstract：

:Epigenetic annotation studies of genetic risk variants for multiple sclerosis (MS) implicate dysfunctional lymphocytes in MS susceptibility; however, the role of central nervous system (CNS) cells remains unclear. We investigated the effect of the risk variant, rs7665090G, located near NFKB1, on astrocytes. We demonstrated that chromatin is accessible at the risk locus, a prerequisite for its impact on astroglial function. The risk variant was associated with increased NF-κB signaling and target gene expression, driving lymphocyte recruitment, in cultured human astrocytes and astrocytes within MS lesions, and with increased lesional lymphocytic infiltrates and lesion sizes. Thus, our study establishes a link between genetic risk for MS (rs7665090G) and dysfunctional astrocyte responses associated with increased CNS access for peripheral immune cells. MS may therefore result from variant-driven dysregulation of the peripheral immune system and of the CNS, where perturbed CNS cell function aids in establishing local autoimmune inflammation.

journal_name

Nat Commun

journal_title

Nature communications

authors

Ponath G,Lincoln MR,Levine-Ritterman M,Park C,Dahlawi S,Mubarak M,Sumida T,Airas L,Zhang S,Isitan C,Nguyen TD,Raine CS,Hafler DA,Pitt D

doi

10.1038/s41467-018-07785-8

subject

Has Abstract

pub_date

2018-12-17 00:00:00

pages

5337

issue

1

issn

2041-1723

pii

10.1038/s41467-018-07785-8

journal_volume

9

pub_type

杂志文章

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