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Introduction  Sjögren's syndrome (SjS) is a systemic autoimmune disease characterized by decreased salivary and lacrimal gland secretions, resulting in severe dry mouth and dry eyes. Recent studies have suggested that T H 17 cells and its signature cytokine IL-17 are involved in the underlying pathogenic mechanisms leading to destructive inflammation and autoimmunity. In the present study, we examined whether IL-27, a natural inhibitor of T H 17 activity, could down-regulate or reverse SjS in C57BL/6.NOD- Aec1Aec2  mice, a model of primary-SjS.    Methods  Recombinant serotype 2 adeno-associated viral (AAV2) vectors expressing either  IL-27  (rAAV2- IL2 7) or  LacZ  (rAAV2- LacZ ) were injected into 6 or 14 week-old C57BL/6.NOD- Aec1Aec2  mice. Changes in IL-27, IL-17, and IL-10 cytokine levels in peripheral blood were determined by ELISAs, while flow cytometry analyses were used to quantify cytokine-positive splenocytes. Histological assessment of salivary glands, anti-nuclear autoantibody (ANA) staining, and stimulated saliva flow rates were used to profile SjS disease severity.    Results  Mice systemically treated with intravenous rAAV2- IL27  injections at either 6 or 14 weeks of age exhibited long-term elevated levels of serum IL-27 with concomitantly reduced levels of IL-17 compared with sera from mice injected with rAAV2- LacZ  or saline out to 20 weeks post-inoculation. Most importantly, disease profiles revealed that rAAV2- IL27  treatment had little effect on lymphocytic focus (LF) scores, but resulted in structural changes in LF, lower titers of ANAs with changes in staining patterns, and a less severe clinical disease as determined by saliva flow rates.    Conclusions  These data support the concept that IL-27, when provided exogenously, can induce a suppressive effect on SjS development and thus may be an effective therapeutic agent for regulating T H 17 pro-inflammatory activity in autoimmune diseases where the T H 17 system has been shown to play an important role in their pathogenesis.

Gene therapy using IL-27 ameliorates Sjögren's syndrome-like autoimmune exocrinopathy