2009
DOI: 10.2353/ajpath.2009.080695
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Role of Plasmacytoid Dendritic Cells for Aberrant Class II Expression in Exocrine Glands from Estrogen-Deficient Mice of Healthy Background

Abstract: Although it has been well documented that aberrant major histocompatibility complex class II molecules may contribute to the development of autoimmune disorders, the precise mechanisms responsible for their tissue-specific expression remain unknown. Here we show that estrogen deficiency induces aberrant class II major histocompatibility complex expression in exocrine glands via interactions between epithelial cells and plasmacytoid dendritic cells. Relatively modest but functionally significant expression leve… Show more

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Cited by 9 publications
(4 citation statements)
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“…Labeling of salivary gland duct cells with antibodies detecting MHC II epitopes has been reported in normal rodent salivary glands [ 29 , 46 ], and in animal models of SS [ 43 ]. More extensive salivary epithelial expression of MHC II antigens may be induced in various experimental conditions, such as interferon-γ treatment [ 46 ] and in estrogen-deficient mice [ 1 ]. Epithelial MHC II expression has been described in normal human salivary glands [ 20 , 51 , 52 ] and is increased in glands of SS patients [ 2 , 13 , 15 , 18 , 49 , 50, 52 ] and patients with various connective tissue diseases [ 28 ].…”
Section: Discussionmentioning
confidence: 99%
“…Labeling of salivary gland duct cells with antibodies detecting MHC II epitopes has been reported in normal rodent salivary glands [ 29 , 46 ], and in animal models of SS [ 43 ]. More extensive salivary epithelial expression of MHC II antigens may be induced in various experimental conditions, such as interferon-γ treatment [ 46 ] and in estrogen-deficient mice [ 1 ]. Epithelial MHC II expression has been described in normal human salivary glands [ 20 , 51 , 52 ] and is increased in glands of SS patients [ 2 , 13 , 15 , 18 , 49 , 50, 52 ] and patients with various connective tissue diseases [ 28 ].…”
Section: Discussionmentioning
confidence: 99%
“…Gene expression of several genes commonly associated with the etiology and autoimmune exocrinopathy in SS were analysed to understand how their expression changed with lymphocytic infiltration and disease progression over time. Quantitative real time-PCR revealed significant up-regulation of IFN-ɣ (Fig 2A) and TNF-α ( Fig 2B), cytokines commonly associated with inflammation in SS patients [34][35][36], as well as upregulation of MHC II, which is associated with increased antigen presentation [37][38][39] (Fig 2C), by 2 M (P<0.01) in male NOD LG when compared to 1 M old male NOD mice. Expression of these genes each increased remarkably between 1-2 M, prior to major lymphocytic infiltration of the LG, and then remained elevated at all time points measured up to 6 M, suggesting a possible causative or initiating role in lymphocytic infiltration.…”
Section: Gene Expression Analysis In Male Nod Mice Lg Shows Early Elementioning
confidence: 94%
“…In particular, a role for estrogen deprivation has been suspected, as the disease often starts after menopause. Estrogen-deficient mice develop a disease similar to primary SS [ 47 ]. Estrogen deficiency induces aberrant class II MHC expression in exocrine glands via interactions between epithelial cells and PDCs.…”
Section: Possible Triggers Of the Ifn Signature In Primary Sjögren's mentioning
confidence: 99%