Friday 16 February 2018, 1.00PM
Speaker(s): Professor Andrew MacDonald, University of Manchester
Although dendritic cells (DCs) are centrally involved in coordination of the immune response during Type 2 inflammation, relatively little is known about how they promote Th2 polarisation. In this context, we have recently found an unexpected role for Type I IFN (IFN-I) in conditioning DCs for optimal induction and development of Type 2 inflammation against either helminths or allergens. Surprisingly, Th2-promoting DCs depended on IFN-I signaling for optimal activation, efficient migration to the draining LN, and effective localization within the T cell zone. Additionally, DCs lacking the IFN-I receptor induced only limited Th2 cytokines in vivo. Together, this suggests a key role for IFN-I responsiveness in enabling Th2 induction by DCs in vivo.
Type 2 inflammation underpins both allergic disease and parasitic worm infections, where one outcome is tissue macrophage proliferation in situ and ‘alternative’ or ‘M2’ activation, primarily in response to the cytokine IL-4. However, we have recently discovered that alveolar macrophages are particularly poorly responsive to Th2 cytokines in vivo, relative to interstitial macrophages or macrophages from other tissue sites. Ongoing work has revealed that alveolar macrophage responsiveness to IL-4 is dictated by the lung environment, though independent of the host microbiota or the prominent lung extracellular matrix components surfactant protein D or mucin 5b. Rather, compared to cavity macrophages, airway macrophages display severely dysregulated metabolism.
Together, these two projects have revealed novel aspects of both initiation and regulation of Type 2 inflammation that may enable rational design of innovative therapies targeting cells or their products to combat Type 2 inflammatory disease.