Dataset Information

Commensal Bacteria-Dependent CD8??+ T Cells in the Intestinal Epithelium Produce Antimicrobial Peptides.

ABSTRACT: The epithelium of the intestine functions as the primary "frontline" physical barrier for protection from enteric microbiota. Intraepithelial lymphocytes (IELs) distributed along the intestinal epithelium are predominantly CD8+ T cells, among which CD8??+ IELs are a large population. In this investigation, the proportion and absolute number of CD8??+ IELs decreased significantly in antibiotic-treated and germ-free mice. Moreover, the number of CD8??+ IELs was correlated closely with the load of commensal microbes, and induced by specific members of commensal bacteria. Microarray analysis revealed that CD8??+ IELs expressed a series of genes encoding potent antimicrobial peptides (AMPs), whereas CD8??+ splenocytes did not. The antimicrobial activity of CD8??+ IELs was confirmed by an antimicrobial-activity assay. In conclusion, microbicidal CD8??+ IELs are regulated by commensal bacteria which, in turn, secrete AMPs that have a vital role in maintaining the homeostasis of the small intestine.

SUBMITTER: Chen B

PROVIDER: S-EPMC5964211 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Commensal Bacteria-Dependent CD8αβ+ T Cells in the Intestinal Epithelium Produce Antimicrobial Peptides.

Chen Banru B Ni Xiang X Sun Rui R Zeng Benhua B Wei Hong H Tian Zhigang Z Wei Haiming H

Frontiers in immunology 20180516

The epithelium of the intestine functions as the primary "frontline" physical barrier for protection from enteric microbiota. Intraepithelial lymphocytes (IELs) distributed along the intestinal epithelium are predominantly CD8+ T cells, among which CD8αβ+ IELs are a large population. In this investigation, the proportion and absolute number of CD8αβ+ IELs decreased significantly in antibiotic-treated and germ-free mice. Moreover, the number of CD8αβ+ I ...[more]

PMID: 29868024

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Project description:Innate lymphoid cells (ILCs) are a recently characterized family of immune cells that have critical roles in cytokine-mediated regulation of intestinal epithelial cell barrier integrity. Alterations in ILC responses are associated with multiple chronic human diseases, including inflammatory bowel disease, implicating a role for ILCs in disease pathogenesis. Owing to an inability to target ILCs selectively, experimental studies assessing ILC function have predominantly used mice lacking adaptive immune cells. However, in lymphocyte-sufficient hosts ILCs are vastly outnumbered by CD4(+) T cells, which express similar profiles of effector cytokines. Therefore, the function of ILCs in the presence of adaptive immunity and their potential to influence adaptive immune cell responses remain unknown. To test this, we used genetic or antibody-mediated depletion strategies to target murine ILCs in the presence of an adaptive immune system. We show that loss of retinoic-acid-receptor-related orphan receptor-?t-positive (ROR?t(+)) ILCs was associated with dysregulated adaptive immune cell responses against commensal bacteria and low-grade systemic inflammation. Remarkably, ILC-mediated regulation of adaptive immune cells occurred independently of interleukin (IL)-17A, IL-22 or IL-23. Genome-wide transcriptional profiling and functional analyses revealed that ROR?t(+) ILCs express major histocompatibility complex class II (MHCII) and can process and present antigen. However, rather than inducing T-cell proliferation, ILCs acted to limit commensal bacteria-specific CD4(+) T-cell responses. Consistent with this, selective deletion of MHCII in murine ROR?t(+) ILCs resulted in dysregulated commensal bacteria-dependent CD4(+) T-cell responses that promoted spontaneous intestinal inflammation. These data identify that ILCs maintain intestinal homeostasis through MHCII-dependent interactions with CD4(+) T cells that limit pathological adaptive immune cell responses to commensal bacteria.

Dataset Information

Commensal Bacteria-Dependent CD8??+ T Cells in the Intestinal Epithelium Produce Antimicrobial Peptides.

Publications

Commensal Bacteria-Dependent CD8αβ<sup>+</sup> T Cells in the Intestinal Epithelium Produce Antimicrobial Peptides.

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