Th17-to-Tfh plasticity during periodontitis limits disease pathology.

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MCCLURE, Flora A, WEMYSS, Kelly, COX, Joshua R, BRIDGEMAN, Hayley M, PRISE, Ian E, KING, James I, JAIGIRDAR, Shafqat, WHELAN, Annie, JONES, Gareth W, GRAINGER, John R, HEPWORTH, Matthew R and KONKEL, Joanne E (2024). Th17-to-Tfh plasticity during periodontitis limits disease pathology. The Journal of experimental medicine, 221 (8): e20232015. [Article]

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Abstract
Th17 cell plasticity is crucial for development of autoinflammatory disease pathology. Periodontitis is a prevalent inflammatory disease where Th17 cells mediate key pathological roles, yet whether they exhibit any functional plasticity remains unexplored. We found that during periodontitis, gingival IL-17 fate-mapped T cells still predominantly produce IL-17A, with little diversification of cytokine production. However, plasticity of IL-17 fate-mapped cells did occur during periodontitis, but in the gingiva draining lymph node. Here, some Th17 cells acquired features of Tfh cells, a functional plasticity that was dependent on IL-6. Notably, Th17-to-Tfh diversification was important to limit periodontitis pathology. Preventing Th17-to-Tfh plasticity resulted in elevated periodontal bone loss that was not simply due to increased proportions of conventional Th17 cells. Instead, loss of Th17-to-Tfh cells resulted in reduced IgG levels within the oral cavity and a failure to restrict the biomass of the oral commensal community. Thus, our data identify a novel protective function for a subset of otherwise pathogenic Th17 cells during periodontitis.
More Information
Official URL:
http://dx.doi.org/10.1084/jem.20232015
Open Access URL:
https://rupress.org/jem/article-pdf/221/8/e2023201...
Open Access Version:
Published version
Uncontrolled Keywords:
Gingiva; Animals; Mice, Inbred C57BL; Mice; Alveolar Bone Loss; Periodontitis; Immunoglobulin G; Interleukin-6; Interleukin-17; Th17 Cells; Cell Plasticity; T Follicular Helper Cells; Th17 Cells; Animals; Periodontitis; Cell Plasticity; Interleukin-17; Mice; Interleukin-6; Mice, Inbred C57BL; T Follicular Helper Cells; Gingiva; Immunoglobulin G; Alveolar Bone Loss; 11 Medical and Health Sciences; Immunology; 32 Biomedical and clinical sciences; 42 Health sciences
Event Location:
United States

Identifiers

Identification Number:
10.1084/jem.20232015
ORCID for Flora A McClure: ORCID iD orcid.org/0000-0003-4366-1506
ORCID for Kelly Wemyss: ORCID iD orcid.org/0000-0003-0385-5920
ORCID for Joshua R Cox: ORCID iD orcid.org/0000-0002-6308-7831
ORCID for Hayley M Bridgeman: ORCID iD orcid.org/0000-0001-7968-7914
ORCID for Ian E Prise: ORCID iD orcid.org/0000-0003-0064-5047
ORCID for James I King: ORCID iD orcid.org/0000-0002-5489-6610
ORCID for Shafqat Jaigirdar: ORCID iD orcid.org/0009-0000-9432-3035
ORCID for Annie Whelan: ORCID iD orcid.org/0000-0003-2266-883X
ORCID for Gareth W Jones: ORCID iD orcid.org/0000-0002-0125-4841
ORCID for John R Grainger: ORCID iD orcid.org/0000-0002-4052-5923
ORCID for Matthew R Hepworth: ORCID iD orcid.org/0000-0002-9613-7858
ORCID for Joanne E Konkel: ORCID iD orcid.org/0000-0002-6525-5499

Library

Item Type:
Article
SWORD Depositor:
Symplectic Elements
Depositing User:
Symplectic Elements
Date Deposited:
13 Jun 2024 16:18
Last Modified:
18 Dec 2024 17:30
Date of first compliant deposit:
13 June 2024
Date of first compliant Open Access:
13 June 2024
Version of first compliant deposit:
Version of Record
URI:
https://shura.shu.ac.uk/id/eprint/33833
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