PXD024126

PXD024126 is an original dataset announced via ProteomeXchange.

Title	Polymorphism in estrogen receptor binding site causes CD2-dependent sex bias in T cell autoimmune diseases
Description	Complex autoimmune diseases are sexually dimorphic. An interplay between predisposing genetics and sex-related factors likely determines the sex discrepancy in the immune response, but conclusive evidence regarding the underlying molecular mechanisms is lacking. Using forward genetics, we positionally identified a polymorphic estrogen receptor binding site that regulates CD2 expression, leading to female-specific differences in mouse models of T cell-dependent autoimmunity. Female mice with reduced CD2 levels displayed a diminished T cell activation and autoimmune T cell response. Mechanistically, CD2 affected LAG-3 expression. Our findings help to explain the sexual dimorphism in human autoimmunity, as CD2 associated with rheumatoid arthritis and its regulation through 17-β-estradiol was conserved in human T cells. Hormonal regulation of CD2 has implications for CD2-targeted therapy. Indeed, anti-CD2 treatment more potently affected female mice. In conclusion, our results demonstrate the relevance of sex-genotype interactions and deliver strong evidence for CD2 as a sex-sensitive predisposing factor in autoimmunity.
HostingRepository	PRIDE
AnnounceDate	2021-07-15
AnnouncementXML	Submission_2021-07-15_06:02:01.506.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pierre Sabatier
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	deaminated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-11 02:25:04	ID requested
⏵ 1	2021-07-15 06:02:01	announced

Dataset with its publication pending

submitter keyword: Estrogen receptor, autoimmune diseases, sexual dimorphism

Rikard Holmdahl
contact affiliation	Division Medical Inflammation Research, Dept. Medical Biochemistry and Biophysics, Karolinska Institute, Sweden The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital), 710004, Xi'an, China
contact email	rikard.holmdahl@ki.se
lab head
Pierre Sabatier
contact affiliation	Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
contact email	pierre.sabatier@ki.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024126
     1. Label: PRIDE project
     2. Name: Polymorphism in estrogen receptor binding site causes CD2-dependent sex bias in T cell autoimmune diseases