This information is current as Monocytes , IL-23 , and TNF-Like 1 A Expression by β Human Memory Th 17 Cells by Inducing IL-1 Hemokinin-1 Favor the Generation of The Tachykinins Substance P and

The nervous system influences immune responses through the release of neural factors such as neuropeptides. Among them, the tachykinin substance P (SP) signals via the neurokinin 1 receptor (NK-1R), which is expressed by various immune cells. We thereby analyzed in this paper whether tachykinins may participate in human CD4 + Th cell polarization. We report that SP and hemokinin-1 (HK-1) upregulate IL-17A and IFN-g production by human memory CD4 + T cells without affecting IL-4 and IL-10 production. SP and HK-1 switch non–Th17-committed CD4 + memory T cells into bona fide Th17 cells and Th1/Th17 cells. In contrast, SP and HK-1 do not modulate the polarization of naive CD4 + T cells. SP-and HK-1–induced Th17 cell generation is mediated through NK-1R and requires the presence of monocytes. SP and HK-1 trigger IL-1b, IL-6, and TNF-a production, upregulate IL-23 production, and enhance TNF-like 1A expression on monocyte surface. Neutralization experiments demonstrated that IL-1b, IL-23, and TNF-like 1A are involved in the SP-and HK-1–induced Th17 cell. The other members of the tachykinin family, neuro-kinins A and B, have no effect on the differentiation of naive and memory T cells. These results thereby show that SP and HK-1 are novel Th17 cell-inducing factors that may act locally on memory T cells to amplify inflammatory responses. N europeptides are nerve-secreted peptides that mediate or modulate neuronal communications and influence brain functions, including memory, learning, analgesia, and food intake. Some neuropeptides also influence innate and adaptive immunity by interacting with immune cells in the lymphoid organs (via the autonomic nervous system), in the bloodstream (via the neuroendocrine system), or at inflammatory sites (via sensory peripheral nerves) (1, 2). Tachykinins are 10–11 aa neuropeptides that share a common C-terminal pentapeptide essential for their biological activities. This family includes four members: substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and the recently identified hemokinin 1 (HK-1) (3). In the CNS, SP is involved in behavior, stress, cognition, and vomiting reflex (3, 4). SP is also released by afferent neurons innervating peripheral tissues and is involved in pain perception, vasodilation, vascular leakiness, and edema (5). In addition to neu-rons, SP is produced by endothelial cells, fibroblasts, and immune cells such as dendritic cells (DCs), macrophages, and lymphocytes (6, 7). HK-1 shows a much broader distribution in peripheral tissues than SP and seems primarily produced by hematopoietic cells (8). HK-1 and SP signal through the neurokinin 1 receptor …