Correction of autophagy impairment inhibits pathology in the NOD.H-2h4 mouse model of primary Sjögren's syndrome.
Animals
Autoantibodies
/ immunology
Autoimmunity
Autophagy
/ immunology
B-Lymphocytes
/ immunology
Disease Models, Animal
Disease Susceptibility
Germinal Center
/ immunology
Immunoglobulin G
/ immunology
Mice
Mice, Inbred MRL lpr
Mice, Inbred NOD
Salivary Glands
/ immunology
Sjogren's Syndrome
/ etiology
T-Lymphocyte Subsets
/ immunology
Autophagy
Phosphopeptide P140
Sjögren's syndrome
Journal
Journal of autoimmunity
ISSN: 1095-9157
Titre abrégé: J Autoimmun
Pays: England
ID NLM: 8812164
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
24
12
2019
revised:
20
01
2020
accepted:
20
01
2020
pubmed:
8
2
2020
medline:
6
7
2021
entrez:
8
2
2020
Statut:
ppublish
Résumé
Dysregulation of autophagy has been implicated in the development of various disease indications including autoimmune diseases. Here we identified hitherto unsuspected molecular alterations of autophagy occurring at an early stage of the macroautophagy pathway in the salivary glands and spleen of NOD.H-2h4 mice that develop a primary Sjögren's-like syndrome. In this study we investigated the capacity of phosphopeptide P140 to correct immune alteration in NOD.H-2h4 mice and the effect on neogenesis of tertiary lymphoid structures in salivary glands, which is hallmark characteristic of SS. Phosphopeptide P140 known to lower excessive autophagy processes, rescued sick NOD.H-2h4 mice from some autophagy defects and significantly reduced formation of tertiary lymphoid structures in salivary glands. Mechanistically, the frequency of activated CD44
Identifiants
pubmed: 32029330
pii: S0896-8411(20)30029-9
doi: 10.1016/j.jaut.2020.102418
pii:
doi:
Substances chimiques
Autoantibodies
0
Immunoglobulin G
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102418Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest EV and AQ are salaried employees and own stocks of AstraZeneka; SM is a co-inventor on patents on P140 peptide. 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.