Aged Sanroque Mice Spontaneously Develop Sjögren's Syndrome-like Disease

Abstract

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder that affects mainly salivary and lacrimal glands, but its cause remains largely unknown. Clinical data indicating that SS occurs in a substantial proportion of patients with lupus points to common pathogenic mechanisms underlying the two diseases. To address this idea, we asked whether SS develops in the lupus-prone mouse strain sanroque (SAN). Owing to hyper-activation of follicular helper T (Tfh) cells, female SAN mice developed lupus-like symptoms at approximately 20 wk of age but there were no signs of SS at that time. However, symptoms typical of SS were evident at approximately 40 wk of age, as judged by reduced saliva flow rate, sialadenitis, and IgG deposits in the salivary glands. Increases in serum titers of SS-related autoantibodies and numbers of autoantibody-secreting cells in cervical lymph nodes (LNs) preceded the pathologic manifestations of SS and were accompanied by expansion of Tfh cells and their downstream effector cells. Thus, our results suggest that chronic dysregulation of Tfh cells in salivary gland-draining LNs is sufficient to drive the development of SS in lupus-prone mice.

RNA binding proteins in the control of autoimmune diseases

“…Also, a subsequent study has shown that sanroque mice develop systemic autoimmunity in a manner partly dependent on Bcl6, which is a master regulator critical for Tfh cells and germinal center formation [58]. Sanroque mice also develop other autoimmune symptoms including Sj€ ogren's syndrome-like symptoms as they age [59].…”

Autoantibody-Mediated Dysfunction of Salivary Glands Leads to Xerostomia in SKG Mice

“…Joint-draining (axillary and inguinal) and cervical lymph node (cLN) cells from SKG mice were analyzed by FACS, as previously described (19). Anti-CD4-PerCP, anti-IFNγ-FITC, and anti-IL-17A-PE were purchased from BD Biosciences (San Jose, CA, USA) or eBioscience (San Diego, CA, USA).…”

“…Submandibular salivary glands were removed post mortem from SKG mice that had been injected with curdlan or PBS 8-10 weeks previously. Paraffin-embedded tissue sections were prepared and stained with H&E as described (19). In some experiments, tissue sections were stained with anti-CD45 IgG (Leica Biosystems, Newcastle, UK) or with anti-mouse IgG-biotin (Sigma-Aldrich), and examined by standard immunohistochemical methods, as described (19).…”

“…Sera were collected from curdlan-or PBS-injected SKG mice, diluted 1:1,000 in PBS, and assayed by standard sandwich ELISA, as described (19). Salivary gland extracts were prepared and used as a source of Ags in ELISA.…”

“…The mouse serum containing the highest titer of each Ab was serially diluted and used as a standard. Ab-secreting cells were enumerated by standard ELISPOT methods (19). Data are presented as numbers of Ab-secreting cells per 2×10 5 cells, with background subtracted.…”