@article{Understanding:2062,
      recid = {2062},
      author = {Howard, Chanie Lai},
      title = {Understanding Human IL-33 Expression in the Lungs During  Inflammation Using a Reporter Model},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2019-12},
      pages = {142},
      abstract = {IL-33 is a tissue-derived cytokine that is abundantly  expressed in the human lung, where it is involved in  pathogen defense and barrier homeostasis. IL-33 alerts  immune cells during allergen exposure and drives the  downstream production of Th2 responses. Notably, while  IL-33 has long been implicated in asthma, the sources of  the cytokine have remained controversial. Here, we probed  the cellular sources of human IL33 using human donor lungs  and show that basal cells and endothelial cells are the  dominant producers. In stark contrast, murine Il33 was  found almost exclusively in lung epithelial type II  pneumocytes. Further, the SNP-containing regulatory  components in the human IL33 locus are not conserved in the  murine locus. Given these differences, we engineered a  novel IL33 reporter mouse containing the regulatory  components from the human locus to reflect human IL33  expression in a murine model. We show that the human IL33  reporter is dramatically reduced by allergic inflammation  and by direct administration of recombinant IL-33 in vivo,  whereas IL33 reporter expression was unaltered airway  epithelium. Extracellular IL-33 negatively regulated  intracellular IL33 levels by inducing mRNA instability in  endothelium, suggesting a mechanism for how IL-33 is able  to dampen its inflammatory effects. Together, these data  reveal a previously unrecognized cellular network comprised  of crosstalk between the lung vasculature and the immune  system that maintains tissue homeostasis and governs  responses in allergic airway disease in humans.},
      url = {http://knowledge.uchicago.edu/record/2062},
      doi = {https://doi.org/10.6082/uchicago.2062},
}