Introduction: Sj�¶grenâ��s syndrome (SjS) is a systemic autoimmune disease characterized by decreased salivary and\r\nlacrimal gland secretions, resulting in severe dry mouth and dry eyes. Recent studies have suggested that TH17\r\ncells and its signature cytokine IL-17 are involved in the underlying pathogenic mechanisms leading to destructive\r\ninflammation and autoimmunity. In the present study, we examined whether IL-27, a natural inhibitor of TH17\r\nactivity, could down-regulate or reverse SjS in C57BL/6.NOD-Aec1Aec2 mice, a model of primary-SjS.\r\nMethods: Recombinant serotype 2 adeno-associated viral (AAV2) vectors expressing either IL-27 (rAAV2-IL27) or\r\nLacZ (rAAV2-LacZ) were injected into 6 or 14 week-old C57BL/6.NOD-Aec1Aec2 mice. Changes in IL-27, IL-17, and\r\nIL-10 cytokine levels in peripheral blood were determined by ELISAs, while flow cytometry analyses were used to\r\nquantify cytokine-positive splenocytes. Histological assessment of salivary glands, anti-nuclear autoantibody (ANA)\r\nstaining, and stimulated saliva flow rates were used to profile SjS disease severity.\r\nResults: Mice systemically treated with intravenous rAAV2-IL27 injections at either 6 or 14 weeks of age exhibited\r\nlong-term elevated levels of serum IL-27 with concomitantly reduced levels of IL-17 compared with sera from mice\r\ninjected with rAAV2-LacZ or saline out to 20 weeks post-inoculation. Most importantly, disease profiles revealed\r\nthat rAAV2-IL27 treatment had little effect on lymphocytic focus (LF) scores, but resulted in structural changes in LF,\r\nlower titers of ANAs with changes in staining patterns, and a less severe clinical disease as determined by saliva\r\nflow rates.\r\nConclusions: These data support the concept that IL-27, when provided exogenously, can induce a suppressive\r\neffect on SjS development and thus may be an effective therapeutic agent for regulating TH17 pro-inflammatory\r\nactivity in autoimmune diseases where the TH17 system has been shown to play an important role in their\r\npathogenesis.
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