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ILC3-induced regulatory T cells are directed by gut microorganisms

Nature Reviews Immunology volume 22, page 207 (2022)Cite this article

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The intestine sustains a state of equilibrium by simultaneously maintaining tolerance to trillions of microorganisms whilst also defending against pathogens. This balance is achieved, in part, by mucosal innate and adaptive immune cells, such as regulatory T (Treg) cells. How gut bacteria might direct mucosal T cells to specific phenotypes is poorly understood, and a recent preprint by Kedmi et al. (not peer-reviewed) seeks to address this question.

Using mice infected with Helicobacter hepaticus, a pathobiont known to induce Treg cells in mesenteric lymph nodes (MLNs) under homeostatic conditions, the authors found that depletion of MHC class II expression from CD11c-expressing cells in these mice reduced the number of Helicobacter hepaticus-specific Treg cells in the MLNs. Strikingly, depletion of conventional dendritic cells failed to phenocopy this effect, which suggests that an alternative CD11c-expressing cell type is involved in the induction of Treg cells by Helicobacter hepaticus in this model. An unbiased approach, using CD11c-Cre fate-mapping mice and CITE-seq technologies, showed that the CD11c-expressing cell type co-expressed RORγt, and these cells were identified in further experiments as group 3 innate lymphoid cells (ILC3s). In keeping with this, depletion of MHC class II expression in RORγt-expressing cells also reduced the number of Helicobacter hepaticus-specific Treg cells. In addition, ablation of CCR7 or αV integrin (ITGAV), which is important for TGFβ activation, in ILC3s also reduced the numbers of Helicobacter hepaticus-specific Treg cells. By contrast, the pathogenic TH17 cell response to Helicobacter hepaticus remained relatively unaltered.

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  1. Preprint Club, University of Oxford, Oxford, UK

    Rahul Ravindran & Emily Thornton

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  1. Rahul Ravindran
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  2. Emily Thornton
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Correspondence to Rahul Ravindran or Emily Thornton.

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Ravindran, R., Thornton, E. ILC3-induced regulatory T cells are directed by gut microorganisms. Nat Rev Immunol 22, 207 (2022). https://doi.org/10.1038/s41577-022-00697-1

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  • DOI: https://doi.org/10.1038/s41577-022-00697-1

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