• IL-13 deficiency exacerbates lung damage and impairs epithelial-derived type 2 molecules during nematode infection.

      Chenery, Alistair L; orcid: 0000-0001-8755-461X; Rosini, Silvia; orcid: 0000-0002-7853-9300; Parkinson, James E; orcid: 0000-0003-4881-5121; Ajendra, Jesuthas; orcid: 0000-0002-9256-5396; Herrera, Jeremy A; orcid: 0000-0003-4845-8494; Lawless, Craig; orcid: 0000-0002-8240-3430; Chan, Brian Hk; orcid: 0000-0002-9451-4621; Loke, P'ng; orcid: 0000-0002-6211-3292; MacDonald, Andrew S; orcid: 0000-0002-5356-1149; Kadler, Karl E; orcid: 0000-0003-4977-4683; et al. (2021-06-14)
      IL-13 is implicated in effective repair after acute lung injury and the pathogenesis of chronic diseases such as allergic asthma. Both these processes involve matrix remodelling, but understanding the specific contribution of IL-13 has been challenging because IL-13 shares receptors and signalling pathways with IL-4. Here, we used infection as a model of acute lung damage comparing responses between WT and IL-13-deficient mice, in which IL-4 signalling is intact. We found that IL-13 played a critical role in limiting tissue injury and haemorrhaging in the lung, and through proteomic and transcriptomic profiling, identified IL-13-dependent changes in matrix and associated regulators. We further showed a requirement for IL-13 in the induction of epithelial-derived type 2 effector molecules such as RELM-α and surfactant protein D. Pathway analyses predicted that IL-13 induced cellular stress responses and regulated lung epithelial cell differentiation by suppression of Foxa2 pathways. Thus, in the context of acute lung damage, IL-13 has tissue-protective functions and regulates epithelial cell responses during type 2 immunity. [Abstract copyright: © 2021 Chenery et al.]
    • Plasmacytoid Dendritic Cells Facilitate Th Cell Cytokine Responses throughout

      Webb, Lauren M; orcid: 0000-0002-1903-7570; Phythian-Adams, Alexander T; orcid: 0000-0003-0426-6562; Costain, Alice H; Brown, Sheila L; Lundie, Rachel J; Forde-Thomas, Josephine; Cook, Peter C; orcid: 0000-0002-5208-4985; Jackson-Jones, Lucy H; orcid: 0000-0003-0608-8966; Marley, Angela K; Smits, Hermelijn H; orcid: 0000-0001-9279-2890; et al. (2021-08-30)
      Plasmacytoid dendritic cells (pDCs) are potent producers of type I IFN (IFN-I) during viral infection and respond to IFN-I in a positive feedback loop that promotes their function. IFN-I shapes dendritic cell responses during helminth infection, impacting their ability to support Th2 responses. However, the role of pDCs in type 2 inflammation is unclear. Previous studies have shown that pDCs are dispensable for hepatic or splenic Th2 responses during the early stages of murine infection with the trematode at the onset of parasite egg laying. However, during infection, an ongoing Th2 response against mature parasite eggs is required to protect the liver and intestine from acute damage and how pDCs participate in immune responses to eggs and adult worms in various tissues beyond acute infection remains unclear. We now show that pDCs are required for optimal Th2 cytokine production in response to eggs in the intestinal-draining mesenteric lymph nodes throughout infection and for egg-specific IFN-γ at later time points of infection. Further, pDC depletion at chronic stages of infection led to increased hepatic and splenic pathology as well as abrogated Th2 cell cytokine production and activation in the liver. In vitro, mesenteric lymph node pDCs supported Th2 cell responses from infection-experienced CD4 T cells, a process dependent on pDC IFN-I responsiveness, yet independent of Ag. Together, these data highlight a previously unappreciated role for pDCs and IFN-I in maintaining and reinforcing type 2 immunity in the lymph nodes and inflamed tissue during helminth infection. [Abstract copyright: Copyright © 2021 The Authors.]