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Laura Schaefer, Claudia M Trujillo-Vargas, Stephen C Pflugfelder, Robert A Britton, Cintia S De Paiva; Sjögren-Syndrome Microbiota Colonization in Germ-Free Mice induces Antigen-Presenting Cell Activation and Production of IL-12. Invest. Ophthalmol. Vis. Sci. 2019;60(9):272.
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© ARVO (1962-2015); The Authors (2016-present)
Sjögren syndrome (SS) is an autoimmune disease causing cellular infiltration of T lymphocytes to the lacrimal and salivary glands. It results in dacryoadenitis and sialadenitis with loss of the exocrine acinar cell function. We have previously shown that SS-patients have reduced diversity of intestinal microbiota and that germ-free mice had a greater frequency of IFN-gamma-producing CD4+ cells and IL-12-producing antigen-presenting cells in cervical lymph nodes (CLN) and lacrimal glands (LG). The purpose of this study was to investigate the effects of humanization of germ-free mice using fecal slurries from SS patients or healthy control subjects on antigen presenting cell activation and IL-12 production.
4-week old female germ-free C57BL-6J mice were humanized with a fecal slurry prepared from either healthy subjects or SS-patients and maintained in the conventional vivarium for another four weeks. At eight weeks of age, CLN single cell suspensions were prepared, and different immune cells subpopulations in LG and CLN were analyzed by flow cytometry.
We observed increased percentages of activated (CD86+) dendritic cells (CD45+MHC II+CD11c+CD11b+ cells) in CLN of germ-free mice humanized with SS stools (P<0.05). This was associated with a statistically significant increased frequency of IL-12-producing DCs and monocytes (CD45+MHC II-CD11c+F4/80+ cells) (P<0.05 for both). SS humanized mice showed decreased levels of Foxp3-expressing CD4+ cells in LGs and CLNs compared to healthy slurry humanized mice (P<0.05).
Our data suggest that SS unbalanced intestinal microbiota conferred an immune dysregulation phenotype and decreased T regulatory cell frequency in ocular surface draining nodes that might contribute to the autoimmune manifestations in the eye. More data are necessary to ascertain the biological relevance of these findings in the function of the T-regulatory cells, corneal barrier disruption and goblet cell numbers in the ocular surface.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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