Inflammation-induced Generation of Splenic Erythroblast-like Ter-Cells Inhibits the Progression of Acute Lung Injury via Artemin.

Abstract

Identifying inflammation-induced leukocyte subsets and their derived circulating factors has been instrumental in understanding the progression of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Nevertheless, how primary inflammation-induced nonleukocyte populations in distal organs contribute to ALI/ARDS remains poorly defined. Here, we report one population of erythroblast-like cells (Ter-cells) deriving from megakaryocyte-erythroid progenitor cells with a unique Ter-119⁺CD45^-CD71⁺ phenotype in ALI/ARDS. Ter-cells induced by the spleen are chemoattracted into the lung to inhibit the progression of ALI by secreting the neurotrophic factor artemin into the blood and BAL fluid. In vivo blockade of Ter-cell-derived artemin aggravates lung injury, and artemin deficiency abolishes Ter-cells' antiinflammatory ability. We confirm the presence of circulating artemin in patients with ARDS and show that significantly elevated artemin correlates with good prognosis. We propose that Ter-cells and the secreted artemin play important roles in ALI/ARDS, with prognostic and therapeutic implications.