T cells are the critical source of IL-4/IL-13 in a mouse model of allergic asthma.

BACKGROUND: IL-4 and IL-13 play a crucial role during allergic asthma. Both cytokines can be produced by T cells and a variety of cell types of the innate immune system. The relative contribution of T-cell-derived vs innate IL-4/IL-13 for allergic inflammation and airway hyperreactivity remains unclear. METHODS: We compared the severity of OVA/alum-induced allergic lung inflammation in WT BALB/c mice to mice that lack expression of IL-4/IL-13 only in T cells (4-13Tko) or in all cell types (4-13ko). RESULTS: T-cell-derived IL-4/IL-13 was required for IgG1 and IgE production, recruitment of eosinophils and basophils to the lung, goblet cell hyperplasia, expression of Muc5ac, Clca3, and RELMß, differentiation of alternatively activated macrophages, and airway hyperreactivity. Interestingly, ILC2 recruitment to the lung occurred independently of T-cell-derived IL-4/IL-13 but was diminished in the absence of IL-4/IL-13 from all cell types. Thus, the number of IL-4/IL-13-competent ILC2s did not correlate with the severity of lung pathology. CONCLUSIONS: Th2 cells appear to be the critical IL-4/IL-13-expressing cell type for the induction of allergic airway inflammation and airway hyperreactivity. The translational perspective of our results indicates that inhibition or reprogramming of Th2 cells may be very effective for the treatment of allergic asthma.

Conditional IL-4/IL-13-deficient mice reveal a critical role of innate immune cells for protective immunity against gastrointestinal helminths.

Approximately one-third of the world population is infected with gastrointestinal helminths. Studies in mouse models have demonstrated that the cytokines interleukin (IL)-4 and IL-13 are essential for worm expulsion, but the critical cellular source of these cytokines is poorly defined. Here, we compared the immune response to Nippostrongylus brasiliensis in wild-type, T cell-specific IL-4/IL-13-deficient and general IL-4/IL-13-deficient mice. We show that T cell-derived IL-4/IL-13 promoted T helper 2 (Th2) polarization in a paracrine manner, differentiation of alternatively activated macrophages, and tissue recruitment of innate effector cells. However, innate IL-4/IL-13 played the critical role for induction of goblet cell hyperplasia and secretion of effector molecules like Mucin5ac and RELMß in the small intestine. Surprisingly, T cell-specific IL-4/IL-13-deficient and wild-type mice cleared the parasite with comparable efficiency, whereas IL-4/IL-13-deficient mice showed impaired expulsion. These findings demonstrate that IL-4/IL-13 produced by cells of the innate immune system is required and sufficient to initiate effective type 2 immune responses resulting in protective immunity against N. brasiliensis.