Tissues can mount in ammatory responses of fundamentally di erent quality with activation of distinct cellular and molecular e ector programs. The “choice” of the right class of respon- se of a particular tissue to a particular challenge determines whether the response will be be- ne cial or harmful. It recently became clear that also healthy tissues sustain innate immune responses in the absence of outside challenges. Such responses contribute to regulation of tissue development and homeostasis.
‘Type 2 immune responses’, de ned by dominant release of the cytokines IL-4, IL-5 and IL-13, are mounted in response to helminthic parasites, ectoparasites (e.g.ticks) and venoms. The term “type 2 response” embraces both the ‘innate’ type 2 responses of tissues and an adap- tive response dominated by TH2 cells and IgE responses. Unbalanced type 2 immune respon- ses are central pathogenic events in allergy, asthma, atopic dermatitis and many brotic di- seases. One of the most urgent questions in medical research therefore is, why tissues mount type 2 responses to particular challenges, but not to others. While adaptive TH2 immunity and IgE responses have been extensively studied, the rules that govern the polarization of innate responses of the di erent tissues toward type 2 remain unclear. However, it is these in- nate tissue responses, which educate emigrating dendritic cells, and thereby dictate the class of adaptive response initiated in tissue-draining lymphatic organs.
FOR2599 is a national research network aiming to elucidate the fundamental mechanisms that induce and regulate type 2 immunity in normal tissues, and in pathologies where type2 immunity is required for protection, or is itself the driver of disease. This is key to unravel causes of inappropriate IgE production in allergic diseases, as well as to understanding type 2 immunity in pathogen defense, brotic and metabolic disease. Insight into control of type 2 responses of tissues is also required to understand how tissues repair and regenerate under the in uence of tissue-speci c protective immune responses.