Redefining intestinal immunity with single-cell transcriptomics

Abstract

The intestinal immune system represents the largest collection of immune cells in the body and is continually exposed to antigens from food and the microbiota. Here we discuss the contribution of single-cell transcriptomics in shaping our understanding of this complex system. We consider the impact on resolving early intestine development, engagement with the neighbouring microbiota, diversity of intestinal immune cells, compartmentalisation within the intestines and interactions with non-immune cells. Finally, we offer a perspective on open questions about gut immunity that evolving single-cell technologies are well placed to address.

Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses

“…Because humans inhale and ingest enormous quantities of exogenous proteins with every breath and mouthful, the respiratory and gastrointestinal immune compartments have evolved to deal with continual and massive antigenic assaults from the outside world. (Immune responses to viral infection of the gastrointestinal mucosa have recently been reviewed, 45 and are not discussed here.) Inhaled and ingested proteins must be identified and either tolerated or attacked and eliminated.…”

Effects of helminths on the human immune response and the microbiome

“…In addition, V(D) J sequencing enables the assessment of clonal expansion and BCR and TCR usage; hence, allowing us to gain unprecedented insights into immune response of different organ systems. The intestinal immune system has been well characterized at a single cell level 117 . This includes samples from in utero intestinal developmental tissues 118 , but has primarily centered on steadystate conditions and inflammatory bowel diseases 117 .…”

“…The intestinal immune system has been well characterized at a single cell level 117 . This includes samples from in utero intestinal developmental tissues 118 , but has primarily centered on steadystate conditions and inflammatory bowel diseases 117 . There have been studies examining the response to the gut microbiota 119 ; however, intestinal immune responses against eukaryotic pathogens remain to be explored by single-cell sequencing.…”

Context-Dependent Regulation of Type17 Immunity by Microbiota at the Intestinal Barrier

“…Pathogenic heterogeneity of IBD significantly contributes to the failure of typically successful novel therapeutics ( 146 ). Recent advances in single-cell sequencing technologies allow for unbiased investigation of distinct cell types within a tissue during health and disease, facilitating our progressive knowledge of the interplay between immune cells and non-immune cells ( 147 ). The integration of multi-omics data, including epigenomics, transcriptomics at the single-cell level, proteomics, metagenomics, and metabolomics will elucidate the crosstalk between different cell types of the intestine and their interactions with gut microbes ( 4 ).…”