Kurzfassung

In the intestine, co-evolution of microbes and vertebrate hosts has established a highlymutualistic relationship. The molecular networks establishing mutualism are only partially understood. It is now widely appreciated that continuous sensing of the indigenous microbiota by immune cells and epithelia promotes tissue homeostasis which may be the primordial function of the immune system at mucosal interfaces. Recent data concerning RORγt⁺ innate lymphocytes has revealed one molecular pathway...In the intestine, co-evolution of microbes and vertebrate hosts has established a highlymutualistic relationship. The molecular networks establishing mutualism are only partially understood. It is now widely appreciated that continuous sensing of the indigenous microbiota by immune cells and epithelia promotes tissue homeostasis which may be the primordial function of the immune system at mucosal interfaces. Recent data concerning RORγt⁺ innate lymphocytes has revealed one molecular pathway required for the mutualistic interaction between microbes and hosts. RORγt⁺ ILC constitutively produce interleukin (IL-)22 in a microbiota-dependent manner. IL-22 exclusively acts on epithelial cells inducing an antimicrobial gene expression program shaping the colonization with benefitial commensals and repelling potential pathogens. A similar molecular network has been identified in invertebrates and it may constitute an evolutionary conserved transcriptional network allowing to establish host-microbe mutualism. The proposal aims to identify specific microbiota and the molecular programs induced by these to regulate function and differentiation of RORγt⁺ ILC. In the second aim, we will analyze the impact of RORγt⁺ ILC on the composition of the colonizing microbiota. These studies may identify molecular circuits selected during evolution to safeguard the mutually benefitial co-existence of microbes and host.» weiterlesen» einklappen