Neuropeptide signaling through neurokinin-1 and neurokinin-2 receptors augments antigen presentation by human dendritic cells

Background: Neurotransmitters, including substance P (SP) and neurokinin A (NKA), are widely distributed in both the central and peripheral nervous system and their receptors, neurokinin-1 receptor (NK1R) and neurokinin-2 receptor (NK2R), are expressed on immune cells. However, the role of the NKA-NK2R axis in immune responses relative to the SP-NK1R signaling cascade has not been elucidated. Objective: We sought to examine the effect of neuropeptide signaling through NK1Rand NK2R on antigen presentation by dendritic cells (DCs) and the subsequent activation of effector Th cells. Methods: Expression levels of NK1R, NK2R, HLA-class II and costimulatory molecules of human MoDCs and cytokine production by birch pollen antigen-specific CD4+ T cells cocultured with MoDCs in the presence of NK1R and NK2R antagonists were evaluated by quantitative RT-PCR, flow cytometry or ELISA. NK1R and NK2R expression in the lung of patients with asthma and hypersensitivity pneumonitis was evaluated by immunohistochemistry. Results: Human MoDCs significantly upregulated NK2R and NK1R expression in response to poly I:C stimulation in a STAT1-dependent manner. Both NK2R and NK1R were expressed on alveolar macrophages and lung DCs from patients with asthma and pneumonitis hypersensitivity. Surface expression levels of HLA-class II and costimulatory molecules on DCs were modulated by NK1R or NK2R antagonists. Activation of birch pollen-derived antigen-specific CD4+ T cells and their production of cytokines including IL-4 and IFN-γ as well as IL-12 production by MoDCs, were suppressed by blocking NK1R or NK2R after in vitro antigen stimulation. Conclusions: NK1R- and NK2R-mediated neuropeptide signaling promotes both innate and acquired immune responses through activation of human DCs

A case of myxoid adrenocortical neoplasm: computed tomography and magnetic resonance imaging characteristics

Myxoid adrenocortical neoplasms are rare; to our knowledge, only 56 cases have been reported in the literature. Therefore, distinguishing benign from malignant cases is challenging. Although the histopathological features of myxoid adrenocortical neoplasia have been amply demonstrated, their imaging characteristics are yet to be reported. We describe here these characteristics for such a neoplasm. Our patient, a 70-year-old male, was found to have a 3-cm left adrenal incidentaloma through a non-enhanced computed tomography. Attenuation measurements were 22 Hounsfield units on precontrast imagery, and percentage enhancement washout was 92%. Magnetic resonance imaging showed no loss of signal intensity in T1-weighted out-of-phase images, but high signal intensity on T2-weighted and diffusion-weighted images. Left adrenalectomy was performed and the pathological diagnosis was confirmed as myxoid adrenocortical neoplasm. The imaging characteristics reported here will be beneficial to the differential diagnosis of myxoid adrenocortical neoplasms based upon image analysis and will help distinguish benign from malignant neoplasms