FRI613 Sex Differences In Human Islet Transcriptional Responses To Inflammation

Disclosure: K.L. Webster: None. W. Wu: None. B. Webb-Robertson: None. E. Nakayasu: None. S. Sarkar: None. C. Evans-Molina: None. S.A. Tersey: None. J. Enriquez: None. S.R. Hammes: None. R.G. Mirmira: None. Higher female incidence of autoimmune disease is often attributed to sex hormone-immune cell interactions or X chromosome immune genes escaping inactivation. Type 1 diabetes (T1D), however, occurs slightly more often in males, and studies show that female sex protects beta cell health under conditions of stress. It is now thought that beta cells themselves trigger loss of immune tolerance in T1D and that the state of beta cell differentiation and health dictates their susceptibility to autoimmunity. Here, we hypothesized that sex influences beta cell response to inflammation during T1D development. We utilized prior bulk RNA sequencing data on human islets from 10 donors (6 males, 4 females) treated for 18h with or without proinflammatory cytokines (PIC: IL-1b, IFNy) to mimic T1D inflammation. Hierarchical clustering grouped samples largely by PIC treatment but also by sex. To identify differentially expressed genes (DEGs) for each sex in response to PIC, we filtered for genes with fold change>1.5 and false discovery rate