Innate immune signaling induces interleukin-7 production from salivary gland cells and accelerates the development of primary Sjögren's syndrome in a mouse model.
Elevated IL-7 in the target tissues is closely associated with multiple autoimmune disorders, including Sjögren's syndrome (SS). We recently found that IL-7 plays an essential role in the development and onset of primary SS (pSS) in C57BL/6.NOD-Aec1Aec2 mice, a well-defined mouse model of prima...
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doaj-47f19b5806b54f06a916b4fa0359c1942020-11-25T02:01:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7760510.1371/journal.pone.0077605Innate immune signaling induces interleukin-7 production from salivary gland cells and accelerates the development of primary Sjögren's syndrome in a mouse model.Jun-O JinYoshinori ShinoharaQing YuElevated IL-7 in the target tissues is closely associated with multiple autoimmune disorders, including Sjögren's syndrome (SS). We recently found that IL-7 plays an essential role in the development and onset of primary SS (pSS) in C57BL/6.NOD-Aec1Aec2 mice, a well-defined mouse model of primary SS. However, environmental signals that cause excessive IL-7 production are not well-characterized. Innate immune signaling plays a critical role in shaping the adaptive immune responses including autoimmune responses. We and others have previously shown that innate immune signaling can induce IL-7 expression in lungs and intestines of C57BL/6 mice. In this study, we characterized the effects of poly I:C, a double-stranded RNA analog and toll-like receptor 3 agonist, on the induction of IL-7 expression in salivary glands and on pSS development. We showed that poly I:C administration to C57BL/6 mice rapidly induced IL-7 expression in the salivary glands in a type 1 IFN- and IFN-γ-dependent manner. Moreover, poly I:C-induced IL-7 contributed to the optimal up-regulation of CXCL9 in the salivary glands, which may subsequently promote recruitment of more IFN-γ-producing T cells. Repeated administration of poly I:C to C57BL/6.NOD-Aec1Aec2 mice accelerated the development of SS-like exocrinopathy, and this effect was abolished by the blockade of IL-7 receptor signaling with a neutralizing antibody. Finally, poly I:C or a combination of IFN-α and IFN-γ induced IL-7 gene expression and protein production in a human salivary gland epithelial cell line. Hence, we demonstrate that IL-7 expression in the salivary gland cells can be induced by poly I:C and delineate a crucial mechanism by which innate immune signals facilitate the development of pSS, which is through induction of IL-7 in the target tissues.http://europepmc.org/articles/PMC3798297?pdf=render |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jun-O Jin Yoshinori Shinohara Qing Yu |
spellingShingle |
Jun-O Jin Yoshinori Shinohara Qing Yu Innate immune signaling induces interleukin-7 production from salivary gland cells and accelerates the development of primary Sjögren's syndrome in a mouse model. PLoS ONE |
author_facet |
Jun-O Jin Yoshinori Shinohara Qing Yu |
author_sort |
Jun-O Jin |
title |
Innate immune signaling induces interleukin-7 production from salivary gland cells and accelerates the development of primary Sjögren's syndrome in a mouse model. |
title_short |
Innate immune signaling induces interleukin-7 production from salivary gland cells and accelerates the development of primary Sjögren's syndrome in a mouse model. |
title_full |
Innate immune signaling induces interleukin-7 production from salivary gland cells and accelerates the development of primary Sjögren's syndrome in a mouse model. |
title_fullStr |
Innate immune signaling induces interleukin-7 production from salivary gland cells and accelerates the development of primary Sjögren's syndrome in a mouse model. |
title_full_unstemmed |
Innate immune signaling induces interleukin-7 production from salivary gland cells and accelerates the development of primary Sjögren's syndrome in a mouse model. |
title_sort |
innate immune signaling induces interleukin-7 production from salivary gland cells and accelerates the development of primary sjögren's syndrome in a mouse model. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Elevated IL-7 in the target tissues is closely associated with multiple autoimmune disorders, including Sjögren's syndrome (SS). We recently found that IL-7 plays an essential role in the development and onset of primary SS (pSS) in C57BL/6.NOD-Aec1Aec2 mice, a well-defined mouse model of primary SS. However, environmental signals that cause excessive IL-7 production are not well-characterized. Innate immune signaling plays a critical role in shaping the adaptive immune responses including autoimmune responses. We and others have previously shown that innate immune signaling can induce IL-7 expression in lungs and intestines of C57BL/6 mice. In this study, we characterized the effects of poly I:C, a double-stranded RNA analog and toll-like receptor 3 agonist, on the induction of IL-7 expression in salivary glands and on pSS development. We showed that poly I:C administration to C57BL/6 mice rapidly induced IL-7 expression in the salivary glands in a type 1 IFN- and IFN-γ-dependent manner. Moreover, poly I:C-induced IL-7 contributed to the optimal up-regulation of CXCL9 in the salivary glands, which may subsequently promote recruitment of more IFN-γ-producing T cells. Repeated administration of poly I:C to C57BL/6.NOD-Aec1Aec2 mice accelerated the development of SS-like exocrinopathy, and this effect was abolished by the blockade of IL-7 receptor signaling with a neutralizing antibody. Finally, poly I:C or a combination of IFN-α and IFN-γ induced IL-7 gene expression and protein production in a human salivary gland epithelial cell line. Hence, we demonstrate that IL-7 expression in the salivary gland cells can be induced by poly I:C and delineate a crucial mechanism by which innate immune signals facilitate the development of pSS, which is through induction of IL-7 in the target tissues. |
url |
http://europepmc.org/articles/PMC3798297?pdf=render |
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