Translocator Protein Deficiency Promotes Splenomegaly with Extramedullary Hematopoiesis after Sepsis.

The translocator protein 18 kDa (TSPO) is expressed in immune cells such as macrophages and hematopoietic progenitors and is involved in modulating innate immune responses. However, a role of TSPO in postsepsis immune dysregulation remains unclear, particularly in the spleen as one of the major immune organs. Here, we investigated the role of TSPO in splenic immune responses following sepsis using TSPO knockout mice 17 days after sepsis induced by cecal ligation and puncture. Results showed that enhanced anxiety-like and depressive-like behaviors as postseptic sequelae were positively correlated with increased spleen weight. Histological analysis revealed that TSPO deletion was associated with splenomegaly with red pulp expansion at the expense of white pulp and increased production of ectopic megakaryocytes. We observed that TSPO deletion led to the gene expression profile enriched in enhanced erythropoiesis and reduced immune responses in the spleen as revealed by bulk RNA-seq analysis. Deconvolution-based immune cell profiling further unraveled that the postseptic spleen of TSPO-knockout mice showed a significant reduction of marker genes for B and T lymphocytes and a further increase of marker genes for other types of cells such as macrophages, neutrophils, erythroblasts, and megakaryocytes in association with spleen weight. The study suggests that TSPO plays a crucial role in maintaining splenic immune homeostasis and hematopoietic balance following sepsis.