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Type 3 innate lymphoid cells direct goblet cell differentiation via the LT-LTβR pathway during Listeria infection

ABSTRACT: As a specialized subset of intestinal epithelial cells (IECs), goblet cells (GCs) play an important role during the antibacterial response via mucin production. However, the regulatory mechanisms involved in GC differentiation and function during infection, particularly the role of immune cell-IEC crosstalk, remain largely unknown. Here, using VillinΔLtbr conditional knockout mice, we demonstrate that LTβR, expressed on IECs, is required for GC hyperplasia and mucin 2 (MUC2) expression during Listeria infection for host defense but not homeostatic maintenance in the naïve state. Analysis of single gene-deficient mice revealed that the ligand lymphotoxin (LT) but not LIGHT and type 3 innate lymphoid cells (ILC3s) but not conventional T cells are required for MUC2-dependent Listeria control. Conditional deficiency of LT in ILC3s further confirmed the importance of LT signals derived from ILC3s. Lack of ILC3-derived LT or IEC-derived LTβR resulted in defective expression of genes related to GC differentiation but was not correlated with IEC proliferation and cell death, which were found to be normal by Ki-67 and Annexin V staining. In addition, the alternative NF-κB signaling pathway (involving RelB) in IECs was found to be required for the expression of GC differentiation-related genes and Muc2 and required for the anti-Listeria response. Therefore, our data together suggest a previously unrecognized ILC3-IEC interaction and LT-LTβR-RelB signaling axis governing GC differentiation and function during Listeria infection for host defense.

ORGANISM(S): Mus musculus

PROVIDER: GSE150071 | GEO | 2020/05/26

REPOSITORIES: GEO

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Group 3 innate lymphoid cells continuously require the transcription factor GATA3 after commitment

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2015-11-23 | E-GEOD-71198 | biostudies-arrayexpress

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2008-12-17 | E-GEOD-11963 | biostudies-arrayexpress

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2019-06-21 | GSE120982 | GEO

RelA and RelB-dependent transcriptome analysis in lymphotoxin-ß receptor stimulated mouse embryonic fibroblasts

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2019-09-16 | GSE137508 | GEO

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2015-11-23 | GSE71198 | GEO

A cis-element at the Rorc locus regulates the development of type 3 innate lymphoid cells

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2023-02-28 | GSE225928 | GEO

Regulation of gene expression in IECs by HDAC3

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