Cystatin C Plays a Sex-Dependent Detrimental Role in Experimental Autoimmune Encephalomyelitis

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Abstract

The cysteine protease inhibitor Cystatin C (CST3) is highly expressed in the brains of multiple sclerosis (MS) patients and C57BL/6J mice with experimental autoimmune encephalomyelitis (EAE; a model of MS), but its roles in the diseases are unknown. Here, we show that CST3 plays a detrimental function in myelin oligodendrocyte glycoprotein 35-55 (MOG35-55)-induced EAE but only in female animals. Female Cst3 null mice display significantly lower clinical signs of disease compared to wild-type (WT) littermates. This difference is associated with reduced interleukin-6 production and lower expression of key proteins (CD80, CD86, major histocompatibility complex [MHC] II, LC3A/B) involved in antigen processing, presentation, and co-stimulation in antigen-presenting cells (APCs). In contrast, male WT and Cst3−/− mice and cells show no differences in EAE signs or APC function. Further, the sex-dependent effect of CST3 in EAE is sensitive to gonadal hormones. Altogether, we have shown that CST3 has a sex-dependent role in MOG35-55-induced EAE.

Detaljer

Författare
  • Vahid Hoghooghi
  • Alexandra L. Palmer
  • Ariana Frederick
  • Yulan Jiang
  • Jessica E. Merkens
  • Anjali Balakrishnan
  • Trisha M. Finlay
  • Anders Grubb
  • Efrat Levy
  • Paul Gordon
  • Frank R. Jirik
  • Minh Dang Nguyen
  • Carol Schuurmans
  • Frank Visser
  • Shannon E. Dunn
  • Shalina S. Ousman
Externa organisationer
  • University of Calgary
  • Sunnybrook Health Sciences Centre
  • Skåne University Hospital
  • NYU Langone
  • Nathan S. Kline Institute for Psychiatric Research
  • Saint Michael's Hospital
Forskningsområden

Nyckelord

Originalspråkengelska
Artikelnummer108236
TidskriftCell Reports
Volym33
Utgåva nummer1
StatusPublished - 2020 okt 6
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa