Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity
Name
nihms-1758271.pdf
Description
Accepted version
Size
3.61 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Schnell, Alexandra
Huang, Linglin
Singer, Meromit
Singaraju, Anvita
Barilla, Rocky M
Regan, Brianna ML
Bollhagen, Alina
Thakore, Pratiksha I
Dionne, Danielle
Delorey, Toni M
Date Issued
2021
Journal
Cell
Publisher
Elsevier BV
Citation
Schnell, Alexandra, Huang, Linglin, Singer, Meromit, Singaraju, Anvita, Barilla, Rocky M et al. 2021. "Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity." Cell, 184 (26).
Version
Author's final manuscript
Abstract
While intestinal Th17 cells are critical for maintaining tissue homeostasis, recent studies have implicated their roles in the development of extra-intestinal autoimmune diseases including multiple sclerosis. However, the mechanisms by which tissue Th17 cells mediate these dichotomous functions remain unknown. Here, we characterized the heterogeneity, plasticity, and migratory phenotypes of tissue Th17 cells in vivo by combined fate mapping with profiling of the transcriptomes and TCR clonotypes of over 84,000 Th17 cells at homeostasis and during CNS autoimmune inflammation. Inter- and intra-organ single-cell analyses revealed a homeostatic, stem-like TCF1+ IL-17+ SLAMF6+ population that traffics to the intestine where it is maintained by the microbiota, providing a ready reservoir for the IL-23-driven generation of encephalitogenic GM-CSF+ IFN-γ+ CXCR6+ T cells. Our study defines a direct in vivo relationship between IL-17+ non-pathogenic and GM-CSF+ and IFN-γ+ pathogenic Th17 populations and provides a mechanism by which homeostatic intestinal Th17 cells direct extra-intestinal autoimmune disease.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELL.2021.11.018
