Tachykinins can partly explain the link within the neuroendocrine‐immune‐hematopoietic axis: novel role for mesenchymal stem cells

Abstract

The tachykinins are among major regulators of bone marrow (BM) functions. The BM is resident to two stem cells: hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). The adult BM has a finite number of HSCs that are required to replenish the immune system throughout life. MSCs surround BM vasculature, while HSCs are located close to the endosteal regions. The mechanisms by which the tachykinins regulate hematopoiesis require further research. Innervated fibers in the BM form synapse‐like structures with MSCs. We propose that tachykinin‐mediated effects on MSCs are relevant to hematopoiesis, because MSCs: 1) generate hematopoietic supporting stromal cells, 2) regulate the movement of cells in and out of the BM, and 3) regulate inflammatory responses in the BM. This study focuses on the truncated tachykinin receptor (NK‐1‐Tr). Its expression and regulation on MSCs mirrors the brain, but contrasts BM stroma. NK‐1‐Tr is predominantly expressed on MSCs. Because of limited receptor desensitization, we propose that NK‐1‐Tr on MSCs could allow rapid responses to the tachykinins so as to maintain the vascular/barrier functions of the BM, regulate immune responses to infectious agents that could be threat to BM failure, and respond to rapid loss of blood. Part of the mechanisms by which the tachykinins regulate MSCs functions involve novel interactions between IFN‐γ and MHC class II. The findings described in this study hold clues to the role of tachykinins on hematopoiesis and adult stem cell functions in the BM. This report adds to an understanding of the crosstalk within the neural‐immune‐hematopoietic axis.