Type 2 inflammation is an inflammatory pathway involving T helper (Th) 2 cells that secrete specific interleukins (IL-4, IL-5, and IL-13), stimulate type 2 immunity (immune memory), and is associated with helminth (parasitic worm) infections and allergy symptoms. Despite this knowledge, how dendritic cells activate Th2 cells to secrete interleukins is not well understood. It is thought that type I interferon (IFN-I) mediates this dendritic cell function. To examine the main factors in the induction of Th2 by dendritic cells, a group of investigators conducted studies using rodent bone marrow dendritic cells generated in vitro, as well in vivo experiments using mouse models of Th2 priming.
One experiment involved culturing dendritic cells with a Th2-inducing antigen (egg antigen from Schistosoma mansoni). The dendritic cells secreted high levels of IFN-I from the S. mansoni exposure. To determine if dendritic cell function depends on their response to IFN-I, mice with dendritic cells unable to respond to IFN-I (i.e., lacking the IFNAR1 subunit of the IFN-I receptor), were exposed to S. mansoni. A significant decrease of IFN-I was evident in the mice exposed to S. mansoni.
Also assessed was the ability of the IFNAR1-negative (IFNAR1-/-) dendritic cells to present and process antigen to T cells. Culturing IFNAR1-/- cells with antigen still lead to T cell proliferation; therefore, the cells did not have a dysfunction or depended on INF-I in regards to processing and presenting antigen in vitro. Next, wild type or IFNAR1-/- dendritic cells were injected subcutaneously into mice. Analysis of the presence of IL-4 by flow cytometry indicated that S. mansoni-activated IFNAR1-/-dendritic cells were not able to induce T-cell secretion of IL-4. Therefore, the capacity of IFNAR1-/- dendritic cells to activate and polarize Th2 cells in vitro, and not in vivo, suggests that responsiveness of dendritic cells to IFN-I is necessary for their migration.
Overall, the results demonstrate that IFN-I signaling is necessary for dendritic cell migration and induction of Th2 in vivo. Therefore, IFN-I is a key factor for regulating Th2 immunity. This new information can be applied for the development of treatment strategies that modulate type 2 responses upon exposure to helminth and other pathogens.
For biomedical research requiring dendritic cells, HemaCare offers top notch, customizable cell products to meet your needs. Call us today at 877-397-3087 to learn more.
Webb LM, e. (2017). Type I interferon is required for T helper (Th) 2 induction by dendritic cells. - PubMed - NCBI. Ncbi.nlm.nih.gov. Retrieved 2 August 2017, from https://www.ncbi.nlm.nih.gov/pubmed/28716804