Maintenance of caecal homeostasis by diverse adaptive immune cells in the rhesus macaque
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Fulltext
Forlagets udgivne version, 16,8 MB, PDF-dokument
Objectives: The caecum bridges the small and large intestine and plays a front-line role in discriminating gastrointestinal antigens. Although dysregulated in acute and chronic conditions, the tissue is often overlooked immunologically. Methods: To address this issue, we applied single-cell transcriptomic-V(D)J sequencing to FACS-isolated CD45+ caecal patch/lamina propria leukocytes from a healthy (5-year-old) female rhesus macaque ex vivo and coupled these data to VDJ deep sequencing reads from haematopoietic tissues. Results: We found caecal NK cells and ILC3s to co-exist with a spectrum of effector T cells partially derived from SOX4+ recent thymic emigrants. Tolerogenic Vγ8Vδ1-T cells, plastic CD4+ T helper cells and GZMK+EOMES+ and TMIGD2+ tissue-resident memory CD8+ T cells were present and differed metabolically. An IL13+GATA3+ Th2 subset expressing eicosanoid pathway enzymes was accompanied by IL1RL1+GATA3+ regulatory T cells and a minor proportion of IgE+ plasma cells (PCs), illustrating tightly regulated type 2 immunity devoid of ILC2s. In terms of B lymphocyte lineages, caecal patch antigen-presenting memory B cells sat alongside germinal centre cells undergoing somatic hypermutation and differentiation into IGF1+ PCs. Prototypic gene expression signatures decreased across PC clusters, and notably, expanded IgA clonotypes could be traced in VDJ deep sequencing reads from additional compartments, including the bone marrow, supporting that these cells contribute a steady stream of systemic antibodies. Conclusions: The data advance our understanding of caecal immunological function, revealing processes involved in barrier maintenance and molecular networks relevant to disease.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e1508 |
| Tidsskrift | Clinical and Translational Immunology |
| Vol/bind | 13 |
| Udgave nummer | 5 |
| Antal sider | 19 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
We thank the staff at the Astrid-Fragaeus Laboratory (Karolinska Institutet, KI), especially Bengt Eriksson, Christian Horner, Pia Ekeland and Jenny Werner. We appreciate the critical input of Tomas Castro Dopico. The data handling was enabled, in part, by Anastasios Glaros and resources provided by the National Academic Infrastructure for Supercomputing in Sweden (NAISS) and the Swedish National Infrastructure for Computing (SNIC) at Uppmax, and partially funded by the Swedish Research Council (Vetenskapsr\u00E5det, VR) through grant agreement no. 2022-06725 and no. 2018-05973. The authors also acknowledge the Eukaryotic Single Cell Genomics (ESCG) facility in Stockholm funded by Science for Life Laboratory, KI Core and StratRegen. Emma Medoc assisted with histology (Biomedicum Histo core, KI). The work was funded by the Swedish Research Council (VR) grants 2017-00968 (awarded to GBKH) and 2018-02381 (awarded to BM).
Funding Information:
We thank the staff at the Astrid\u2010Fragaeus Laboratory (Karolinska Institutet, KI), especially Bengt Eriksson, Christian Horner, Pia Ekeland and Jenny Werner. We appreciate the critical input of Tomas Castro Dopico. The data handling was enabled, in part, by Anastasios Glaros and resources provided by the National Academic Infrastructure for Supercomputing in Sweden (NAISS) and the Swedish National Infrastructure for Computing (SNIC) at Uppmax, and partially funded by the Swedish Research Council (Vetenskapsr\u00E5det, VR) through grant agreement no. 2022\u201006725 and no. 2018\u201005973. The authors also acknowledge the Eukaryotic Single Cell Genomics (ESCG) facility in Stockholm funded by Science for Life Laboratory, KI Core and StratRegen. Emma Medoc assisted with histology (Biomedicum Histo core, KI). The work was funded by the Swedish Research Council (VR) grants 2017\u201000968 (awarded to GBKH) and 2018\u201002381 (awarded to BM).
Publisher Copyright:
© 2024 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
ID: 393151823