MANF regulates splenic macrophage differentiation in mice

Splenic immune cells, especially macrophages, play a key role in multiple pathological processes. With a proved anti-inflammatory and immunoregulatory function of mesencephalicastrocyte-derived neurotrophic factor (MANF) in inflammatory disorders, how MANF affects splenic immune cells in physiological and pathophysiological situations is still unknown. In this study, we constructed mono-macrophage-specific MANF knockout (Mempty set MANF(-/-)) mice and found the increased splenic M1 macrophages, but no significant change of splenic morphology and size compared with wild type (WT) mice. Also, we established the pathophysiological situation of carbon tetrachloride (CCl4)-induced hepatic fibrosis. Under the hepatic fibrosis, splenic M2 macrophages and CD138(+) plasma cells were significantly increased in Mempty set MANF(-/-) mice. Consistently, we found the increased TGF-beta 1 level in serum and spleen of Mempty set MANF(-/-) mice as well. Mono-macrophage-specific MANF knockout did not affect the number of splenic T and B cells under both the normal and hepatic fibrosis conditions. Our results suggest a distinct regulation of MANF on splenic immune cells and a specific regulation of MANF on the differentiation of splenic macrophages, which may exert a significant impact on physiological and pathophysiological processes of the spleen.