C9orf72 in myeloid cells suppresses STING-induced inflammation

In this study we report that loss of C9orf72 expression in myeloid cells drives STING/type I interferon mediated autoimmunity and enhanced tumor immunity in mice. Additionally, we show that the immunophenotypic signature identified in C9orf72-/- mice is present in blood derived macrophages, whole blood and autopsy brain tissue from C9orf72 repeat expansion ALS/FTD patients. Overall design: DCs: 4 WT & 4 C9orf72 KO; Bcells, CD4, CD8 & CD11B: 4 WT, 4 Cx3Cr1-CRE conditional C9orf72 KO, 3 C9orf72 KO & 4 C9orf72 KO x Golden Ticket (Tmem173 KO); hMDMs: 5 Normal Controls, 5 with C9ORF72 expansion & 5 Sporadic ALS; hMDMs_H151: 2 C9ORF72 expansion samples treated with H151 & the same 2 C9ORF72 expansion samples treated with DMSO