Human TLR8 induces inflammatory bone marrow erythromyeloblastic islands and anemia in SLE-prone mice

• DOI: 10.26508/lsa.202302241
• Publication Date: 2023-07-26T18:20:22Z
• Authors: Naomi I Maria; Julien Papoin; Chirag Raparia; Zeguo Sun; Rachel Josselsohn; Ailing Lu; Hani Katerji; Mahrukh M Syeda; David Polsky; Robert Paulson; Theodosia Kalfa; Betsy J Barnes; Weijia Zhang; Lionel Blanc; Anne Davidson
• Keywords: Bone marrow failure

Anemia commonly occurs in systemic lupus erythematosus, a disease characterized by innate immune activation nucleic acids. Overactivation of cytoplasmic sensors self-DNA or RNA can cause erythroid cell death, while sparing other hematopoietic lineages. Whereas chronic inflammation is involved this mechanism, less known about the impact erythematosus on BM erythropoietic niche. We discovered that expression endosomal ssRNA sensor human TLR8 induces fatal anemia Sle1.Yaa mice. observed was associated with decrease erythromyeloblastic islands and block differentiation at CFU-E to proerythroblast transition BM. Single-cell RNAseq analyses isolated from TLR8-expressing mice revealed genes essential central macrophage functions including adhesion provision nutrients were down-regulated. Although compensatory stress erythropoiesis occurred spleen, red blood half-life decreased because hemophagocytosis. These data implicate as an additional receptor whose overactivation causes acquired failure via myeloid dysregulation.