2018
DOI: 10.3390/ijms19103259
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Type I Interferon Signaling Is Required for Dacryoadenitis in the Nonobese Diabetic Mouse Model of Sjögren Syndrome

Abstract: Nonobese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity similar to human Sjögren syndrome. In both humans and NOD mice, the early immune response that drives T-cell infiltration into lacrimal and salivary glands is poorly understood. In NOD mice, lacrimal gland autoimmunity spontaneously occurs only in males with testosterone playing a role in promoting lacrimal gland inflammation, while female lacrimal glands are protected by regulatory T cells (Tregs). The mechanisms of th… Show more

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Cited by 12 publications
(24 citation statements)
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“…Lacrimal gland inflammation was markedly diminished with little to no inflammation detected in the glands from male Tlr7 KO mice compared to WT male mice ( Figure 2 A,B). Neither WT nor Tlr7 KO female mice developed lacrimal gland inflammation ( Figure 2 C,D) in accordance with the known male-specific occurrence of spontaneous lacrimal gland autoimmunity in NOD mice [ 19 , 23 ]. In contrast, females developed focal sialadenitis to a similar degree regardless of the presence or absence of TLR7 ( Figure 2 E,F).…”
Section: Resultssupporting
confidence: 81%
“…Lacrimal gland inflammation was markedly diminished with little to no inflammation detected in the glands from male Tlr7 KO mice compared to WT male mice ( Figure 2 A,B). Neither WT nor Tlr7 KO female mice developed lacrimal gland inflammation ( Figure 2 C,D) in accordance with the known male-specific occurrence of spontaneous lacrimal gland autoimmunity in NOD mice [ 19 , 23 ]. In contrast, females developed focal sialadenitis to a similar degree regardless of the presence or absence of TLR7 ( Figure 2 E,F).…”
Section: Resultssupporting
confidence: 81%
“…Other proteins like IFN inducible guanylate binding protein 1 and CD45 + cell infiltration are corelated and may be analyzed by the degree of CD45 + infiltration in the major SGs of pSS patients [ 107 ]. CCL9 and CCL19 expression is up-regulated in the salivary (SG) and LGs (LG) of NOD and C57BL/6.NOD- Aec1Aec2 mice during disease onset, inducing other potentially disease relevant genes such as Epsti1 and Ubd that show enhanced activity in the LGs of male mice [ 109 , 114 ]. IL-7, known to cause increased production of IFN-γ and CXCR3 via upregulation of Th1 cells, has been shown to accelerate the development of SS [ 115 ].…”
Section: Adaptive Immune Cellsmentioning
confidence: 99%
“…In contrast, the inflammation of lacrimal and salivary glands tends to occur with more absolute sex-specificity. Moreover, evidence supports different interferon (IFN)-mediated immune pathways required for lacrimal and salivary gland disease with male-specific lacrimal gland inflammation dependent on type I IFN signaling 41 and female-specific salivary gland inflammation dependent on type II IFN signaling 42 . In T1D, the roles of IFN signaling are more complex, but neither type I nor type II IFN signaling is absolutely required for T1D development in either sex 43 .…”
Section: Discussionmentioning
confidence: 99%