Gastrointestinal microbiota and immune cells interact closely and display regional specificity; however, little is known about how these communities differ with location. Here, we simultaneously assess microbiota and single immune cells across the healthy, adult human colon, with paired characterization of immune cells in the mesenteric lymph nodes, to delineate colonic immune niches at steady state. We describe distinct helper T cell activation and migration profiles along the colon and characterize the transcriptional adaptation trajectory of regulatory T cells between lymphoid tissue and colon. Finally, we show increasing B cell accumulation, clonal expansion and mutational frequency from the cecum to the sigmoid colon and link this to the increasing number of reactive bacterial species.
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Raw sequencing data files are available at ArrayExpress (accession nos. E-MTAB-8007, E-MTAB-8474, E-MTAB-8476, E-MTAB-8484 and E-MTAB-8486). Sequencing data for the microbiome are available at MGnify. (ERA numbers are listed in Supplementary Table 6.) Processed scRNA-seq data are available for online visualization and download at the Gut Cell Atlas (https://www.gutcellatlas.org/).
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We acknowledge the support received from the Wellcome Sanger Cytometry Core Facility, Cellular Genetics Informatics team and Core DNA Pipelines. We thank F. Rouhani and T. Castro-Dopico for insightful discussions about project and experimental design and K. Mahbubani for help with the collection of human tissue. We acknowledge J. Eliasova for the graphical images. This research was supported by funding from the Wellcome Trust (grant no. WT206194 to S.A.T.) and the European Research Council (grant no. 646794 ThDEFINE to S.A.T.). K.R.J. holds a Non-Stipendiary Junior Research Fellowship from Christ’s College, University of Cambridge. T.G. was funded by the European Union’s H2020 research and innovation programme ‘ENLIGHT-TEN’ under Marie Skłodowska-Curie grant agreement no. 675395. H.W.K. was funded by a Sir Henry Wellcome Postdoctoral Fellowship (grant no. 213555/Z/18/Z). B.R.B. was funded by the NIHR Cambridge Biomedical Research Centre (grant no. RG92051). We thank the deceased organ donors, donor families and the Cambridge Biorepository for Translational Medicine for access to the tissue samples. This publication is part of the Human Cell Atlas (https://www.humancellatlas.org/publications/).
S.C.F. and T.D.L. are either employees of, or consultants to, Microbiotica.
Editor recognition statement Zoltan Fehervari was the primary editor(s) on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.
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James, K.R., Gomes, T., Elmentaite, R. et al. Distinct microbial and immune niches of the human colon. Nat Immunol 21, 343–353 (2020). https://doi.org/10.1038/s41590-020-0602-z
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