Open AccessCellular context of IL-33 expression dictates impact on anti-helminth immunity
Author(s) -
Li-Yin Hung,
Yukinori Tanaka,
Karl Herbine,
Christopher Pastore,
Brenal K. Singh,
Annabel A. Ferguson,
Nisha Vora,
Bonnie Douglas,
Kelly Zullo,
Edward M. Behrens,
Tiffany Tan,
Michael A. Kohanski,
Paul J. Bryce,
Cailu Lin,
Taku Kambayashi,
Danielle R. Reed,
Breann L. Brown,
Noam A. Cohen,
De’Broski R. Herbert
Publication year - 2020
Publication title -
science immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.83
H-Index - 51
ISSN - 2470-9468
DOI - 10.1126/sciimmunol.abc6259
Subject(s) - context (archaeology) , biology , immunity , immunology , helminths , expression (computer science) , helminth infections , immune system , microbiology and biotechnology , computer science , paleontology , programming language
Interleukin-33 (IL-33) is a pleiotropic cytokine that can promote type 2 inflammation but also drives immunoregulation through Foxp3 + T reg expansion. How IL-33 is exported from cells to serve this dual role in immunosuppression and inflammation remains unclear. Here, we demonstrate that the biological consequences of IL-33 activity are dictated by its cellular source. Whereas IL-33 derived from epithelial cells stimulates group 2 innate lymphoid cell (ILC2)-driven type 2 immunity and parasite clearance, we report that IL-33 derived from myeloid antigen-presenting cells (APCs) suppresses host-protective inflammatory responses. Conditional deletion of IL-33 in CD11c-expressing cells resulted in lowered numbers of intestinal Foxp3 + T reg cells that express the transcription factor GATA3 and the IL-33 receptor ST2, causing elevated IL-5 and IL-13 production and accelerated anti-helminth immunity. We demonstrate that cell-intrinsic IL-33 promoted mouse dendritic cells (DCs) to express the pore-forming protein perforin-2, which may function as a conduit on the plasma membrane facilitating IL-33 export. Lack of perforin-2 in DCs blocked the proliferative expansion of the ST2 + Foxp3 + T reg subset. We propose that perforin-2 can provide a plasma membrane conduit in DCs that promotes the export of IL-33, contributing to mucosal immunoregulation under steady-state and infectious conditions.