Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

Activation of Innate Immunity and Sjgren's Syndrome Development.

Nandula1,  Seshagiri Rao, Scindia2,  Yogesh M., Bagavant1,  Harini, Deshmukh2,  Umesh S.

University of Virginia, Charlottesville, VA
University of Virginia


Previously our laboratory has demonstrated that activation of innate immunity through toll-like receptor 3 (TLR3) agonist poly IC causes an acute loss of salivary gland function. This study was undertaken to investigate the effects of innate immunity activation through TLR dependent and TLR independent pathways on development of Sjögren's Syndrome (SS) in experimental mouse model systems.


To determine the role of TLR mediated innate immunity activation in SS, female NZB/W F1 mice were injected with TLR3 agonist, poly IC. To investigate TLR independent pathways, female NZM2758 mice were injected with alum, which activates innate immunity through the inflammasome pathway. Submandibular glands (SMG) were analyzed for sialadenitis and lymphocytic infiltrates were characterized by flow cytometry and immunohistochemistry. Gene expression levels of inflammatory cytokines and chemokines were determined by real time PCR. Mice were monitored for salivary gland hypofunction by checking pilocarpine induced saliva flow.


Within 2 weeks of poly IC treatment, the SMG showed evidence for lymphocytic infiltration. The dominant cell types infiltrating the SMG at early stages were NK cells and dendritic cells, which correlated with the chemokine pattern induced by poly IC. At later time points, T-B cell aggregates were seen within the SMG with significantly higher levels of IL-12A, IL-21 and IL-21R gene expression. Characterization of CD4+ T cells within the infiltrates showed presence of ICOS+CXCR5+ cells indicative of the T follicular helper cell phenotype. SMG from poly IC treated mice showed IgM and IgG deposition. Although the severity of sialadenitis increased with time, it did not correlate with loss of function. In the inflammasome mediated innate immunity activation model, mice showed evidence for loss of glandular function by 8–10 weeks after alum treatment. At this time point no lymphocytic foci were seen in the SMG. By 4–5 months, SMG from alum treated mice showed evidence for sialadenitis. Interestingly, this did not translate in to further worsening of glandular function.


Our data clearly demonstrates that activation of innate immunity accelerates the development of SS. Although the characteristics of disease development vary depending upon the innate stimulus, the models reinforce a lack of correlation between extent of of sialadenitis and severity of glandular dysfunction, as observed in SS patients. The ability of alum to induce SS in genetically susceptible mouse strains suggests that exposure to aluminum compounds can be a novel risk factor for SS.

This work is supported by grants from Sjögren's Syndrome Foundation USA and NIDCR.

To cite this abstract, please use the following information:
Nandula, Seshagiri Rao, Scindia, Yogesh M., Bagavant, Harini, Deshmukh, Umesh S.; Activation of Innate Immunity and Sjgren's Syndrome Development. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1883
DOI: 10.1002/art.29648

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