FOR2599National research network for investigation of induction and regulation of innate type 2 immune responses of tissues

Our Mission

Tissues can mount inflammatory responses of fundamentally different quality with activation of distinct cellular and molecular effector programs. The “choice” of the right class of response of a particular tissue to a particular challenge determines whether the response will be beneficial 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’, defined 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 adaptive response dominated by TH2 cells and IgE responses. Unbalanced type 2 immune responses are central pathogenic events in allergy, asthma, atopic dermatitis and many fibrotic diseases. 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 different tissues toward type 2 remain unclear. However, it is these innate 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, fibrotic and metabolic disease. Insight into control of type 2 responses of tissues is also required to understand how tissues repair and regenerate under the influence of tissue-specific protective immune responses.