Ruffilli I
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Clin Ter. 2014;165(6):e464-9. doi: 10.7417/CT.2014.1793.
Interferon (IFN)-γ-induced protein 10 (IP-10) and its receptor, chemokine (C-X-C motif) receptor (CXCR)3, appear to contribute to the pathogenesis of Sjögren's syndrome (SS). The expression of IP-10 and CXCR3 is increased, in salivary glands from SS patients, both in the ductal epithelium adjacent to lymphoid infiltrates and in lymphocytes. IFN-γ induces the production of high levels of IP-10 and monokine induced by IFN-γ (MIG) proteins from cultured SS salivary epithelial cells. Under the influence of IFN-γ, IP-10 secreted by salivary cells, recruits T helper (Th)1 lymphocytes that may be responsible for enhanced IFN-γ, which in turn stimulates a further IP-10 secretion from epithelial cells creating an amplification feedback loop and perpetuating the autoimmune process. Determination of high level of IP-10 in tears and saliva is therefore a marker of a Th1 orientated immune response. In experimental settings IP-10 antagonists can ameliorate the progression of autoimmune sialadenitis, providing a new therapeutic approach to SS. Further studies are needed to investigate whether IP-10 is a novel therapeutic target in SS in humans.
干扰素（IFN）-γ诱导蛋白10（IP-10）及其受体趋化因子（C-X-C基序）受体（CXCR）3似乎在干燥综合征（SS）的发病机制中起作用。在SS患者的唾液腺中，IP-10和CXCR3的表达增加，在邻近淋巴浸润的导管上皮和淋巴细胞中均如此。IFN-γ可诱导培养的SS唾液上皮细胞产生高水平的IP-10和IFN-γ诱导的单核因子（MIG）蛋白。在IFN-γ的影响下，唾液细胞分泌的IP-10招募可能负责增强IFN-γ的辅助性T（Th）1淋巴细胞，这反过来又刺激上皮细胞进一步分泌IP-10，从而形成一个放大反馈回路并使自身免疫过程持续存在。因此，泪液和唾液中高水平的IP-10测定是Th1型免疫反应的一个标志物。在实验环境中，IP-10拮抗剂可改善自身免疫性涎腺炎的进展，为SS提供一种新的治疗方法。需要进一步研究以调查IP-10是否是人类SS的一个新的治疗靶点。
