LymphoILC3

Cells expressing the nuclear hormone receptor RORgt play an essential role in mucosal immunity, producing the pro-inflammatory cytokines IL-17, IL-22 and GM-CSF to maintain the equilibrium between the host and its symbiotic microbiota. However, these cytokines are also involved in autoimmune inflammatory pathologies, and RORgt has become an important pharmacological target to modulate inflammation. Whereas most T cells are induced to express RORgt by microbiota, type 3 innate lymphoid cells (ILC3s) are programmed to express RORgt, constitutively produce IL-22, and are critical early in mucosal responses to infection and injury. Therefore, ILC3s are expected to play a major role in the regulation of adaptive immune responses not only to microbiota and infection, but also to auto-antigens, allergens and dietary metabolites. However, a mouse model allowing for the specific ablation of ILC3s to address their role in the development and regulation of adaptive immune responses has been lacking so far. We have now generated a mouse line that allows for the specific and time-controlled ablation of ILC3s. We will investigate the mechanisms by which ILC3s regulate adaptive immunity, which include control of antigen presenting cells, microbiota and metabolism. These studies will pave the way for the manipulation of ILC3s, for boosting defense or mitigating immunopathology, as well as for the regulation of adaptive immunity during vaccination and allergy.