I02 RORa and notch play important roles in type-2 ILC development

Abstract

Dysregulation of type-2 immune responses, characterised by production of IL-4, IL-5, IL-9, and IL-13, underlies many aspects of allergic asthma. It is becoming increasingly clear that innate cell types, in addition to the classical Th2 cells, can produce these cytokines and that they may play critical roles in the initiation of the type-2 response. Using Il13-eGFP reporter mice, we identified and characterised a new innate type-2 immune effector leukocyte that we named the nuocyte. Nuocytes can be defined as lineage negative (linneg), ICOS+IL- 17BR+ckitvariableT1/ST2 variable and represent the predominant early source of IL-13 during helminth infection with Nippostrongylus brasiliensis. Type-2 ILCs also expand in experimental models of asthma, where they may represent an important source of type-2 cytokines. We have now shown that nuocytes belong to the lymphoid lineage and can be included in the type-2 innate lymphoid cell (ILC) family. These type-2 ILCs develop from common lymphoid progenitors under signals from IL-7 and IL-33. Furthermore, we demonstrate that, like T cells, nuocytes require Notch signaling for development. We have gone on to show that the transcription factor RORa, a relative of RORgt, plays an important role in nuocyte development.