The crosstalk between the nervous, immune and endocrine systems and its role for immune diseases

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We investigated the crosstalk between nervous, immune and endocrine systems. Neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are essential factors for the development of the nervous system. However, here, we demonstrate gene expression of neuropeptide, neurotrophins and their receptors in Th1 and Th2 cells induced from naive CD4^+CD45RB^+ T cells from OVA-specific D011.10 TCR transgenic mice. Interestingly, preproenkephalin (PPE) gene is specifically induced in Th2 cells but not in Th1 cells. Moreover, it is demonstrated that TrkC gene, which encodes a high affinity receptor for NT-3, was selectively expressed in Th2 cells, but not in Th1 and naive CD4^+ T cells. Expression of the TrkC gene was markedly augmented by addition of anti-IFN-g mAb into the culture, whereas it was blocked by anti-IL-4 mAb. Moreover, NT-3 synergistically enhanced anti-CD3 mAb-induced IL-4 production by Th2 cells, but did not affect IFN-g production by Th1 cells. These data suggest that NT-3, through its receptor TrkC, plays a critical role in regulating the Th1/Th2 balance.We also found that Th2 cells but not Th1 cells expressed functional P450ssc and 20a-HSD genes, which are critical enzymes for steroidgenesis and metabolite. Addition of cholesterol into Th2 cell-culture resulted in generation of steroid precursor, prognenolone. Th2 cells did not metabolite prognenolone to generate progesterone by themselves. However, if they were co-existed with stroma cells which express functional 3b-HSD gene, significant levels of progesterone were produced. Moreover, progesterone is shown to stimulate the polarization of naive Th cells into Th2 cells. Thus, it was demonstrated that immune steroid produced by Th2 cells is involved in the regulation of immune balance.