Cystatin C Plays a Sex-Dependent Detrimental Role in Experimental Autoimmune Encephalomyelitis
Authors: Frank R Jirik
Alexandra L Palmer
Yulan Jiang
Carol Schuurmans
Paul Gordon
Efrat Levy
Trisha M Finlay
Minh Dang Nguyen
Shalina S Ousman
Anjali Balakrishnan
Shannon E Dunn
Jessica E Merkens
Frank Visser
Anders Grubb
Ariana Frederick
Vahid Hoghooghi
Journal: Cell Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CST3; Cystatin C; antigen-presenting cells; experimental allergic encephalomyelitis; experimental autoimmune encephalomyelitis
Affiliations: Department of Neuroscience, Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada., Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada., Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada., Department of Clinical Chemistry, Lund University Hospital, SE 221 85 Lund, Sweden., Department of Psychiatry and Department of Biochemistry & Molecular Pharmacology, Neuroscience Institute, NYU Langone Health, New York, NY, USA; Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA., Cumming School of Medicine Centre for Health Genomics and Informatics, University of Calgary, Calgary, AB T2N 4N1, Canada., Department of Biochemistry & Molecular Biology, and Department of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada., Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Cell Biology & Anatomy, and Department of Biochemistry & Molecular Biology, Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada., Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada., Department of Immunology, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, St. Michael's Hospital, University of Toronto, Toronto, ON M5B 1W8, Canada., Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Cell Biology & Anatomy, Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: .

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. 

Retracted: No

PubPeer comments:
 Hello, Thank you for your intriguing research. B7 is depicted on T cells and CD80 86 on APC in the graphical abstract. While CD80 and CD86 are also known as B7.1 2. The correct ligand for B7 (CD80 86) expressed on CD4 T cells is CD28. Please correct this error from the abstract. ,