Open AccessRegulation of intestinal immunity and tissue repair by enteric glia
Author(s) -
Fränze Progatzky,
Michael Shapiro,
Song Hui Chng,
Bethania García-Cassani,
Cajsa Classon,
Selin Sevgi,
Anna Laddach,
Ana Carina Bon-Frauches,
Reena Lasrado,
Maryam Rahim,
Eleni-Maria Amaniti,
Stefan Boeing,
Kathleen Shah,
Lewis J. Entwistle,
Alejandro SuárezBonnet,
Mark S. Wilson,
Brigitta Stockinger,
Vassilis Pachnis
Publication year - 2021
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-021-04006-z
Subject(s) - immunity , microbiology and biotechnology , enteric nervous system , enteric bacteria , enteric virus , biology , chemistry , immune system , immunology , neuroscience , biochemistry , escherichia coli , gene
Tissue maintenance and repair depend on the integrated activity of multiple cell types 1 . Whereas the contributions of epithelial 2,3 , immune 4,5 and stromal cells 6,7 in intestinal tissue integrity are well understood, the role of intrinsic neuroglia networks remains largely unknown. Here we uncover important roles of enteric glial cells (EGCs) in intestinal homeostasis, immunity and tissue repair. We demonstrate that infection of mice with Heligmosomoides polygyrus leads to enteric gliosis and the upregulation of an interferon gamma (IFNγ) gene signature. IFNγ-dependent gene modules were also induced in EGCs from patients with inflammatory bowel disease 8 . Single-cell transcriptomics analysis of the tunica muscularis showed that glia-specific abrogation of IFNγ signalling leads to tissue-wide activation of pro-inflammatory transcriptional programs. Furthermore, disruption of the IFNγ-EGC signalling axis enhanced the inflammatory and granulomatous response of the tunica muscularis to helminths. Mechanistically, we show that the upregulation of Cxcl10 is an early immediate response of EGCs to IFNγ signalling and provide evidence that this chemokine and the downstream amplification of IFNγ signalling in the tunica muscularis are required for a measured inflammatory response to helminths and resolution of the granulomatous pathology. Our study demonstrates that IFNγ signalling in enteric glia is central to intestinal homeostasis and reveals critical roles of the IFNγ-EGC-CXCL10 axis in immune response and tissue repair after infectious challenge.