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Cintia S de Paiva, Mahira Zaheer, Fang Bian, Alton Swennes, Robert A Britton, Stephen C Pflugfelder; Protective Role of Commensal Microbiota in the CD25KO Sjögren Syndrome Mouse Model. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of the gut microbiota in the appearance and development of dacryoadenitis in a model of Sjögren Syndrome.
Eight- week old Germ-free (GF) CD25 knock-out (KO) mice of both genders were compared to CD25KO mice raised in specific pathogen free (SPF) conditions. Corneal barrier function was assessed by fluorescent Oregon-Green Dextran dye staining. Eyes and adnexae were excised and prepared for either histology or frozen sections. Conjunctival goblet cell density was counted in periodic acid Schiff stained sections. Total cell infiltrates were visualized in histologic sections stained for H&E. CD4, CD8 and B cell infiltration were quantified by flow cytometry. CD4+T cells were isolated from cervical lymph nodes (CLN) and adoptively transferred into RAG1KO recipients. T helper (Th) phenotype in lacrimal gland (LG) and CLN of recipients was investigated by intracellular staining 5 weeks post-transfer.
GF CD25KO mice have significantly lower number of goblet cells and significantly greater corneal barrier disruption and LG infiltration than CD25KO SPF mice (P<0.05 for all). There were similar percentages of CD4+, and CD8+ T and B cells in the LG, but lower percentage (%) of CD4+ IFN-gamma+ (21.55% vs.60.9%), CD4+IL-17+ (0.33 vs. 44.8%) cells in GF compared to SPF CD25KO. In contrast, RAG1KO recipients of adoptively transferred GF CD25KO CD4+T cells had significantly greater total LG infiltration and loss of acini than recipients of SPF CD25KO CD4+T cells. Greater number of CD45+CD4+ cells were observed in LG than CLN, demonstrating greater homing to the LG. This was accompanied by greater percentage of CD4+ IFN-gamma+ (55.5% vs. 32%, P=0.02) and CD4+IL-17+ (4.91% vs. 1.08%, P=0.03) cells in the LG of GF recipients compared to SPF recipients.
Lack of commensal bacteria accelerates the onset and severity of dacryoadenitis and generates autoreactive CD4+T cells with greater pathogenicity. These results indicate the commensal bacteria or products secreted by them have immunoregulatory properties that protect exocrine glands in the CD25KO SS model.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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