The thymus at the crossroad of neuroimmune interactions

The numerous relationships existing between the nervous and the immune systems suggest that the neural networks present in the intrathymic microenvironment may influence T-cell development. We previously reported that thymic neural-crest-derived stromal cells are involved in a neural differentiation pathway and are able to produce neurotrophic factors and neurokines that are in turn able to increase and/or modulate thymic-stromal cell neuronal phenotype. We also showed that EGF promotes a neural phenotype in thymic epithelial cells by enhancing the expression of neuronal-specific markers, neurotransmitters, and neuropoietic cytokines, such as IL-6 and CNTF. More recently we showed that the effect of EGF in directing thymic epithelial cells toward a neural-oriented cell fate is mediated by modulating the expression of genes directly involved in neurotypic differentiation (i.e., thrombospondin-1). EGF-induced regulation of stromal cells may also affect T-cell differentiation, as we observed that an EGF-pretreatment reduces the ability of thymic epithelial cells to sustain thymocyte differentiation in vitro. Finally, we demonstrated that a complex network involving the neurotrophin BDNF and its specific receptors may have a role in sustaining thymocyte precursor survival and supporting the thymocyte differentiation process. All together, our results suggest that the thymus may be the site of integration of different neuroimmune networks that are potentially involved in the regulation of thymocyte survival and/or differentiation.