Dataset Information

Commensal bacteria maintain a Qa-1^b-restricted unconventional CD8⁺ T population in gut epithelium.

ABSTRACT: Intestinal intraepithelial lymphocytes (IELs) are characterized by an unusual phenotype and developmental pathway, yet their specific ligands and functions remain largely unknown. Here by analysis of QFL T cells, a population of CD8⁺ T cells critical for monitoring the MHC I antigen processing pathway, we established that unconventional Qa-1^b-restricted CD8⁺ T cells are abundant in intestinal epithelium. We found that QFL T cells showed a Qa-1^b-dependent unconventional phenotype in the spleen and small intestine of naïve wild-type mice. The splenic QFL T cells showed innate-like functionality exemplified by rapid response to cytokines or antigens, while the gut population was refractory to stimuli. Microbiota was required for the maintenance, but not the initial gut homing of QFL T cells. Moreover, monocolonization with Pediococcus pentosaceus, which expresses a peptide that cross-activated QFL T cells, was sufficient to maintain QFL T cells in the intestine. Thus, microbiota is critical for shaping the Qa-1^b-restricted IEL landscape.

SUBMITTER: Guan J

PROVIDER: S-EPMC10735220 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Commensal bacteria maintain a Qa-1b-restricted unconventional CD8+ T population in gut epithelium.

Guan Jian J Peske J David JD Manoharan Valerio Michael M Park Chansu C Robey Ellen A EA Sadegh-Nasseri Scheherazade S

eLife 20231221

Intestinal intraepithelial lymphocytes (IELs) are characterized by an unusual phenotype and developmental pathway, yet their specific ligands and functions remain largely unknown. Here by analysis of QFL T cells, a population of CD8+ T cells critical for monitoring the MHC I antigen processing pathway, we established that unconventional Qa-1b-restricted CD8+ T cells are abundant in intestinal epithelium. We found that QFL T cells showed a Qa-1b-depende ...[more]

PMID: 38127067

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Project description:Aim: Microbial colonization of the intestine in newborns is a critical event that regulates host physiology with lifelong consequences. However, there is a need to identify microbial molecules and mechanisms that play a role in this process. We aimed to elucidate the effects of flagellin, an important immunomodulatory component involved in bacterial motility, on intestinal epithelial functions. Methods: Germfree mice were colonized with synthetic bacterial communities, including a flagellated mouse gut isolate of Escherichia coli or a ΔfliC mutant thereof that lacks flagella. The offspring of these mice were studied at 7 days of age by single-cell RNA sequencing of epithelial cells isolated from the small intestine. Results: Enterococcus faecalis was the most dominant species in the small intestine of newborn mice. Blautia pseudococcoides was detected at low relative abundances. Colonization by either E. coli strain reduced the relative abundance of E. faecalis to 10% on average, and E. coli became the dominant member, with no substantial differences between mice colonized with the wildtype or mutant strain. The distribution of cell types within the small intestinal epithelium was skewed toward specialized cells (goblet, enteroendocrine, stem cells) at the expense of enterocytes in mice colonized with flagellated bacteria. These mice were characterized by higher expression of genes involved in cell-cell interactions (Npl, Epcam) and responses to infection (Ctsl) in enterocytes and enhanced translation (ribosomal proteins) in stem cells. In contrast, genes involved in lipid homeostasis (transport and metabolism; Apoc 2/4, Dgat2, Fabp 1/2, Mttp) in all cell types and inflammatory and androgen-related pathways in specialized cell types were less expressed in epithelial cells exposed to wildtype E. coli. Conclusion: These findings suggest that early life exposure to flagellated commensal bacteria influences cellular processes underlying tissue metabolism and remodeling in the small intestine.

Dataset Information

Commensal bacteria maintain a Qa-1^b-restricted unconventional CD8⁺ T population in gut epithelium.

Publications

Commensal bacteria maintain a Qa-1<sup>b</sup>-restricted unconventional CD8<sup>+</sup> T population in gut epithelium.

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Dataset Information

Commensal bacteria maintain a Qa-1b-restricted unconventional CD8+ T population in gut epithelium.

Publications

Commensal bacteria maintain a Qa-1&lt;sup&gt;b&lt;/sup&gt;-restricted unconventional CD8&lt;sup&gt;+&lt;/sup&gt; T population in gut epithelium.

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OmicsDI is part of the ELIXIR infrastructure

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Commensal bacteria maintain a Qa-1^b-restricted unconventional CD8⁺ T population in gut epithelium.

Commensal bacteria maintain a Qa-1<sup>b</sup>-restricted unconventional CD8<sup>+</sup> T population in gut epithelium.