| First Author | Fernandez Lahore G | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 5565 |
| PubMed ID | 34552089 | Mgi Jnum | J:313291 |
| Mgi Id | MGI:6787661 | Doi | 10.1038/s41467-021-25828-5 |
| Citation | Fernandez Lahore G, et al. (2021) Polymorphic estrogen receptor binding site causes Cd2-dependent sex bias in the susceptibility to autoimmune diseases. Nat Commun 12(1):5565 |
| abstractText | Complex autoimmune diseases are sexually dimorphic. An interplay between predisposing genetics and sex-related factors probably controls the sex discrepancy in the immune response, but the underlying mechanisms are unclear. Here we positionally identify a polymorphic estrogen receptor binding site that regulates Cd2 expression, leading to female-specific differences in T cell-dependent mouse models of autoimmunity. Female mice with reduced Cd2 expression have impaired autoreactive T cell responses. T cells lacking Cd2 costimulation upregulate inhibitory Lag-3. These findings help explain sexual dimorphism in human autoimmunity, as we find that CD2 polymorphisms are associated with rheumatoid arthritis and 17-beta-estradiol-regulation of CD2 is conserved in human T cells. Hormonal regulation of CD2 might have implications for CD2-targeted therapy, as anti-Cd2 treatment more potently affects T cells in female mice. These results demonstrate the relevance of sex-genotype interactions, providing strong evidence for CD2 as a sex-sensitive predisposing factor in autoimmunity. |
