Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology.
Sjögren’s syndrome
autoimmunity
fibroblasts
tertiary lymphoid structures
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
02 07 2019
02 07 2019
Historique:
pubmed:
20
6
2019
medline:
31
3
2020
entrez:
20
6
2019
Statut:
ppublish
Résumé
Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases.
Identifiants
pubmed: 31213547
pii: 1905301116
doi: 10.1073/pnas.1905301116
pmc: PMC6613169
doi:
Substances chimiques
Interleukin-13
0
Interleukins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13490-13497Subventions
Organisme : Arthritis Research UK
ID : G0601156
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 21236
Pays : United Kingdom
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/K000527/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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