Ab0136 interferon Stimulated Genes in Cd4 T Cells Are Associated With Pyroptosis Pathways in Patients With Lupus

Abstract

BackgroundSingle cell RNA sequencing (scRNA-seq) of kidney tissues in patients with lupus has led to landscape of complete cellular composition and states for immune and non-immune cells. These studies suggested type I interferon (IFN) signatures prime inflammatory responses. However, there is a lack of knowledge regarding the characteristics of subsets of IFN stimulating genes (ISG) high expressed cells.ObjectivesHere we investigated immune cell compositions between peripheral blood mononuclear cells (PBMCs), skin and kidney tissues in patients with lupus using scRNA-seq. We characterized a subset of ISG high CD4 T cells, which are commonly expressed across PBMCs, skins and kidneys of lupus but not skins of healthy.MethodsscRNA-seq dataset of PBMCs, skin and kidney tissues in patients with lupus were collected. We integrated and analyzed immune cell compositions from this scRNA-seq dataset. We focused on subset of ISG high expressed CD4 T cells and characterized top 200 genes of this subset.ResultsThere is one subset of ISG high expressed CD4 T cells in the lupus PBMCs, kidneys, and skins but not in the healthy skins. This ISG high expressed CD4 T cells have the greatest number of type I interferon signatures and gasdermin D gene, which is related to pyroptosis of cells, among top 200 genes. We further investigated pyroptosis pathway genes in the subsets of CD3 T cells. Interestingly, the subset of ISG high expressed CD4 T cells have most increased pyroptosis related upstream regulating genes including IRF1, GBP1, CASP4 and CASP1. Furthermore, this subset highly expressed inflammasome gene such as NLRC5 not NLRP3ConclusionThere are ISG high expressed CD4 T cells across tissues of lupus. Those cells highly expressed pyroptosis pathway related genes. Further investigation is needed to characterize association between ISG and pyroptosis.Reference[1]Arazi A, Rao DA, Berthier CC, Davidson A, Liu Y, Hoover PJ, et al. The immune cell landscape in kidneys of patients with lupus nephritis. Nat Immunol 2019;20:902-14.Acknowledgements:NIL.Disclosure of InterestsNone Declared.