TLR7 Signaling Drives the Development of Sjögren's Syndrome.
Sjögren’s syndrome (SS)
TLR7
TLR8-deficient mice
autoimmunity
dendritic cells
innate immunity
transgenic mice
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
04
03
2021
accepted:
27
04
2021
entrez:
10
6
2021
pubmed:
11
6
2021
medline:
25
2
2023
Statut:
epublish
Résumé
Sjögren's syndrome (SS) is a chronic systemic autoimmune disease that affects predominately salivary and lacrimal glands. SS can occur alone or in combination with another autoimmune disease like systemic lupus erythematosus (SLE). Here we report that TLR7 signaling drives the development of SS since TLR8-deficient (TLR8ko) mice that develop lupus due to increased TLR7 signaling by dendritic cells, also develop an age-dependent secondary pathology similar to associated SS. The SS phenotype in TLR8ko mice is manifested by sialadenitis, increased anti-SSA and anti-SSB autoantibody production, immune complex deposition and increased cytokine production in salivary glands, as well as lung inflammation. Moreover, ectopic lymphoid structures characterized by B/T aggregates, formation of high endothelial venules and the presence of dendritic cells are formed in the salivary glands of TLR8ko mice. Interestingly, all these phenotypes are abrogated in double TLR7/8-deficient mice, suggesting that the SS phenotype in TLR8-deficient mice is TLR7-dependent. In addition, evaluation of TLR7 and inflammatory markers in the salivary glands of primary SS patients revealed significantly increased
Identifiants
pubmed: 34108972
doi: 10.3389/fimmu.2021.676010
pmc: PMC8183380
doi:
Substances chimiques
Chemokines
0
Cytokines
0
Toll-Like Receptor 7
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
676010Informations de copyright
Copyright © 2021 Wang, Roussel-Queval, Chasson, Hanna Kazazian, Marcadet, Nezos, Sieweke, Mavragani and Alexopoulou.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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