Gut Helicobacter presentation by multiple dendritic cell subsets enables context-specific regulatory T cell generation
- Washington University in St Louis, United States
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States
- University of Pittsburgh, United States
Abstract
Generation of tolerogenic peripheral regulatory T (pTreg) cells is commonly thought to involve CD103+ gut dendritic cells (DCs), yet their role in commensal-reactive pTreg development is unclear. Using two Helicobacter-specific T cell receptor (TCR) transgenic mouse lines, we found that both CD103+ and CD103– migratory, but not resident, DCs from the colon-draining mesenteric lymph node presented Helicobacter antigens to T cells ex vivo. Loss of most CD103+ migratory DCs in vivo using murine genetic models did not affect the frequency of Helicobacter-specific pTreg cell generation or induce compensatory tolerogenic changes in the remaining CD103– DCs. By contrast, activation in a Th1-promoting niche in vivo blocked Helicobacter-specific pTreg generation. Thus, these data suggest a model where DC-mediated effector T cell differentiation is 'dominant', necessitating that all DC subsets presenting antigen are permissive for pTreg cell induction to maintain gut tolerance.
Data availability
16S rRNA sequencing data has been deposited in ENA (PRJEB42640).
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Fecal 16S samples from CD207-DTA and Irf8-Delta149en cDC deficient miceEuropean Nucleotide Archive, PRJEB42640.
Article and author information
Author details
Emilie V Russler-Germain
Funding
National Institutes of Health (R01 AI079187)
- Chyi-Song Hsieh
National Institutes of Health (R01 AI136515)
- Chyi-Song Hsieh
Burroughs Wellcome Fund
- Chyi-Song Hsieh
National Institutes of Health (F30 DK111071)
- Emilie V Russler-Germain
National Institutes of Health (T32 GM007200)
- Emilie V Russler-Germain
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were performed in strict accordance with the guidelines of the Institutional Animal Care and Use Committee at Washington University (Protocol Number: 20170036).
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Gut Helicobacter presentation by multiple dendritic cell subsets enables context-specific regulatory T cell generation
eLife 10:e54792.
https://doi.org/10.7554/eLife.54792
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