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

Hoghooghi, Vahid ; Palmer, Alexandra L. ; Frederick, Ariana ; Jiang, Yulan ; Merkens, Jessica E. ; Balakrishnan, Anjali ; Finlay, Trisha M. ; Grubb, Anders LU orcid ; Levy, Efrat and Gordon, Paul , et al. (2020) In Cell Reports 33(1).
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
keywords
antigen-presenting cells, CST3, Cystatin C, experimental allergic encephalomyelitis, experimental autoimmune encephalomyelitis, multiple sclerosis, sex effect, sex hormones
in
Cell Reports
volume
33
issue
1
article number
108236
publisher
Cell Press
external identifiers
  • scopus:85092297053
  • pmid:33027652
ISSN
2211-1247
DOI
10.1016/j.celrep.2020.108236
language
English
LU publication?
no
id
a25745c1-ef11-4660-8b6f-6593555ee69a
date added to LUP
2020-11-06 08:38:36
date last changed
2024-06-27 01:23:01
@article{a25745c1-ef11-4660-8b6f-6593555ee69a,
  abstract     = {{<p>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 (MOG<sub>35-55</sub>)-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<sup>−/−</sup> 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 MOG<sub>35-55</sub>-induced EAE.</p>}},
  author       = {{Hoghooghi, Vahid and Palmer, Alexandra L. and Frederick, Ariana and Jiang, Yulan and Merkens, Jessica E. and Balakrishnan, Anjali and Finlay, Trisha M. and Grubb, Anders and Levy, Efrat and Gordon, Paul and Jirik, Frank R. and Nguyen, Minh Dang and Schuurmans, Carol and Visser, Frank and Dunn, Shannon E. and Ousman, Shalina S.}},
  issn         = {{2211-1247}},
  keywords     = {{antigen-presenting cells; CST3; Cystatin C; experimental allergic encephalomyelitis; experimental autoimmune encephalomyelitis; multiple sclerosis; sex effect; sex hormones}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{1}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Cystatin C Plays a Sex-Dependent Detrimental Role in Experimental Autoimmune Encephalomyelitis}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2020.108236}},
  doi          = {{10.1016/j.celrep.2020.108236}},
  volume       = {{33}},
  year         = {{2020}},
}