Shani Gal-Oz, PhD
Brigham and Women's Hospital
Rheumatology, Inflammation and Immunity
Shani T. Gal-Oz, Alev Baysoy, Brinda Vijaykumar, Barbara Maier, Hideyuki Yoshida, Kumba Seddu, Nitzan Elbaz, Charles Czysz, Or Zuk, Barbara E. Stranger, Hadas Ner-Gaon, Sara Mostafavi, the Immunological Genome Project, Christophe Benoist, Michael Brenner, Tal Shay
The mammalian immune system displays widespread differences between males and females (sexual-dimorphism). In human, it manifests as more frequent and severe infectious diseases in males and, on the other hand, higher rates of autoimmune disease in females. Yet, the mechanisms are not fully understood.
In mice, using bulk-RNA sequencing, we showed that sex differences in the naïve immune system are unique to macrophages (out of 11 studied immune cell types). These naïve female macrophages expressed higher levels of interferon signature genes. Accordingly, the female in-vivo response to interferon was stronger. Next, we leveraged single-cell transcriptomics to look for contributing cell sub-populations and heterogeneity among individual cells throughout the response to interferon stimulation. Comparing macrophages, CD4 T and B lymphocytes, we showed that the kinetics of the response is cell-type specific, and within each cell type, female cells respond faster than male cells. These results pointed towards macrophages and interferon as key players in immune sexual-dimorphism. Suggesting that female higher baseline activation and faster response to interferon might contribute to their better first line of defense but may come with the cost of autoimmunity risk.
Interferon pathway is highly correlated with autoimmune diseases. Therefore, as a postdoctoral fellow in Prof. Michael Brenner’s lab at Brigham and Women’s Hospital, I am now leveraging the knowledge and skills to study the relationship between sex differences, interferon pathway, and autoimmunity in human. Focusing on Rheumatoid Arthritis (RA) as a representative autoimmune disease with higher female-male ratios. As a part of a collaborative project (AMP RA/SLE), transcriptomic and proteomic dataset of >80 male and female RA patients and control was generated.
We plan to re-analyze the described dataset looking for sex differences, specifically asking how the inflamed tissue is different between the sexes in terms of cellular composition, interferon pathway expression and sex-specific cell sub-populations.