Abstract：
: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 CD44high/CD62Llow CD4+ T cell populations was significantly decreased and this reduction was correlated with an increased number of CD44low/CD62Lhigh resting T cells. The CD8 T cell compartment was not affected. P140 down-regulated the maturation and differentiation of B cells into plasma cells, and decreased IgG and autoantibody secretion. It had no effect on germinal centers B cells (B220+ FAS+GL-7+) that are an important compound of the B cell humoral immune response. Together with previous data generated in MRL/lpr mice that develop some features of Sjögren's syndrome associated to other inflammatory and autoimmune defects, our present findings strongly reinforce the potential of autophagy modulators, such as P140, for treating patients with Sjögren's syndrome.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Voynova E,Lefebvre F,Qadri A,Muller Sdoi
10.1016/j.jaut.2020.102418subject
Has Abstractpub_date
2020-03-01 00:00:00pages
102418eissn
0896-8411issn
1095-9157pii
S0896-8411(20)30029-9journal_volume
108pub_type
杂志文章abstract：:TREX1 encodes a major cellular DNA exonuclease. Mutations of this gene in human cause cellular accumulation of DNA that triggers autoimmune diseases including Aicardi-Goutieres Syndrome (AGS) and systemic lupus erythematosus (SLE). We created a lupus mouse model by engineering a D18 N mutation in the Trex1 gene which ...
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journal_title：Journal of autoimmunity
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journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
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journal_title：Journal of autoimmunity
pub_type： 历史文章,杂志文章,评审
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journal_title：Journal of autoimmunity
pub_type： 杂志文章
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更新日期：2019-12-01 00:00:00
abstract：:Lupus erythematosus (LE) is an inflammatory connective tissue disease of generalized autoimmunity characterized by pathogenic autoantibodies and immune complexes, attributed to loss of immune tolerance. Cutaneous involvement, which appears in the majority of patients with the disease, can present as LE-specific or LE-...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
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