| First Author | Han S | Year | 2022 |
| Journal | Elife | Volume | 11 |
| PubMed ID | 36264674 | Mgi Jnum | J:336681 |
| Mgi Id | MGI:7366595 | Doi | 10.7554/eLife.76205 |
| Citation | Han S, et al. (2022) A novel monocyte differentiation pattern in pristane-induced lupus with diffuse alveolar hemorrhage. Elife 11:e76205 |
| abstractText | Pristane causes chronic peritoneal inflammation resulting in lupus, which in C57BL/6 mice is complicated by lung microvascular injury and diffuse alveolar hemorrhage (DAH). Mineral oil (MO) also causes inflammation, but not lupus or DAH. Since monocyte depletion prevents DAH, we examined the role of monocytes in the disease. Impaired bone marrow (BM) monocyte egress in Ccr2-/- mice abolished DAH, confirming the importance of monocyte recruitment to the lung. Circulating Ly6C(hi) monocytes from pristane-treated mice exhibited increased annexin-V staining in comparison with MO-treated controls without evidence of apoptosis, suggesting that pristane alters the distribution of phosphatidylserine in the plasma membrane before or shortly after monocyte egress from the BM. Plasma membrane asymmetry also was impaired in Nr4a1-regulated Ly6C(lo/-) 'patrolling' monocytes, which are derived from Ly6C(hi) precursors. Patrolling Ly6C(lo/-) monocytes normally promote endothelial repair, but their phenotype was altered in pristane-treated mice. In contrast to MO-treated controls, Nr4a1-regulated Ly6C(lo/-) monocytes from pristane-treated mice were CD138(+), expressed more TremL4, a protein that amplifies TLR7 signaling, and exuberantly produced TNFalpha in response to TLR7 stimulation. TremL4 expression on these novel CD138(+) monocytes was regulated by Nr4a1. Thus, monocyte CD138, high TremL4 expression, and annexin-V staining may define an activated/inflammatory subtype of patrolling monocytes associated with DAH susceptibility. By altering monocyte development, pristane exposure may generate activated Ly6C(hi) and Ly6C(lo/-) monocytes, contributing to lung microvascular endothelial injury and DAH susceptibility. |
