Innate lymphoid cells (ILC) are members of the lymphoid lineage with roles in immunity, regulating tissue homeostasis and inflammation. ILC2, in addition to the classical Th2 cells, produce the type-2 cytokines IL-4, IL-5, IL-9, and IL-13, and play critical roles in the initiation of the type-2 response. ILC subsets are particularly prevalent at mucosal surfaces, which are constantly exposed to infectious agents in the external environment. ILC2 rapidly secrete high levels of IL-5 and IL-13, resulting in eosinophilia and mucus hyper-secretion, and provide a potent innate effector response to combat intestinal parasitic helminth infections and inappropriately during asthma and allergy. In recent studies we have demonstrated that ILC2 increase in human skin from AD patients and shown that ILC2 can be induced in human skin by challenge with the common allergen house dust mite. These skin ILC2 were highly responsive to prostaglandin D2 that bound to the CRTH2 to induce high levels of IL-5 and IL-13 production, highlighting the opportunity for potential therapeutic intervention with CRTH2 or PGD2 inhibitors.
Ongoing studies using new reagents, including ILC2-deficient mice, are aimed at dissecting the roles of ILC2 in their interactions with innate and adaptive immune responses. Notably we have demonstrated that ILC2 can potentiate the adaptive Th2 response. Intranasal administration of protease allergen papain was used to stimulate ILC2 and Th2 cells, causing allergic lung inflammation. This activation of Th2 cells was severely impaired in ILC2-deficient mice. Notably, ILC2-derived IL-13 was critical for the induction of inflammation due to IL-13 promoting migration of activated lung dendritic cells into the draining lymph node to prime Th2 cell differentiation.
Disclosure of Interest A. Mckenzie Grant/Research support from: Funding from Janssen
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