Identification and characterization of CXCL13 producers in bone tissue

Abstract The bone serves as a reservoir for several immune cell subsets in response to the low-energy status such as fasting. We previously demonstrated that naïve B cells transiently migrate from Peyer’s patches to the bone marrow during fasting in mice. This B-cell dynamics is attributed to upregulation of CXCL13 in the bone during fasting. However, CXCL13 producers in the bone remain to be determined. We observed that lineage-negative population from the bone is responsible for Cxcl13 expression. To further clarify the CXCL13 producers, we performed single-cell RNA-sequencing of bone linage-negative cells from Ad libitum-fed mice and fasting mice. UMAP analysis manifested that the numbers of fibroblasts and multipotent stem cells (MSCs) were increased in the fasting group. Interestingly, Cxcl13-producing cells were identified as osteogenic-MSCs characterized by expressions of Sca-1 (immature cells marker), Sema3c, and Dcn (osteogenic cells maker). This population also expressed an inflammatory cytokine Il6. Meanwhile, mature osteoblasts and chondrocytes expressed neither Cxcl13 nor Il6. Furthermore, co-culture with the plasma from fasting mice upregulated CXCL13 expression in osteogenic-MSCs in vitro, suggesting that a soluble factor(s) in the circulation induces CXCL13. Taken together, osteogenic-MSCs in the bone may sense nutritional status and produce CXCL13 to regulate naïve B-cell dynamics along the gut-bone axis. The pathophysiological role of CXCL13-producing osteogenic-MSCs is currently under investigation. none