Bradshaw Elizabeth M, Raddassi Khadir, Elyaman Wassim, Orban Tihamer, Gottlieb Peter A, Kent Sally C, Hafler David A
Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
J Immunol. 2009 Oct 1;183(7):4432-9. doi: 10.4049/jimmunol.0900576. Epub 2009 Sep 11.
Autoimmune diseases including type 1 diabetes (T1D) are thought to have a Th1/Th17 bias. The underlying mechanisms driving the activation and differentiation of these proinflammatory T cells are unknown. We examined the monocytes isolated directly from the blood of T1D patients and found they spontaneously secreted the proinflammatory cytokines IL-1beta and IL-6, which are known to induce and expand Th17 cells. Moreover, these in vivo-activated monocytes from T1D subjects induced more IL-17-secreting cells from memory T cells compared with monocytes from healthy control subjects. The induction of IL-17-secreting T cells by monocytes from T1D subjects was reduced in vitro with a combination of an IL-6-blocking Ab and IL-1R antagonist. In this study, we report a significant although modest increase in the frequency of IL-17-secreting cells in lymphocytes from long-term patients with T1D compared with healthy controls. These data suggest that the innate immune system in T1D may drive the adaptive immune system by expanding the Th17 population of effector T cells.
包括1型糖尿病（T1D）在内的自身免疫性疾病被认为存在Th1/Th17偏向。驱动这些促炎T细胞活化和分化的潜在机制尚不清楚。我们检测了直接从T1D患者血液中分离出的单核细胞，发现它们会自发分泌促炎细胞因子IL-1β和IL-6，已知这两种细胞因子可诱导和扩增Th17细胞。此外，与健康对照受试者的单核细胞相比，这些来自T1D受试者的体内活化单核细胞能从记忆T细胞诱导产生更多分泌IL-17的细胞。用IL-6阻断抗体和IL-1R拮抗剂联合处理后，T1D受试者的单核细胞在体外对分泌IL-17的T细胞的诱导作用减弱。在本研究中，我们报告称，与健康对照相比，长期T1D患者淋巴细胞中分泌IL-17细胞的频率虽有显著但适度的增加。这些数据表明，T1D中的固有免疫系统可能通过扩增效应T细胞的Th17群体来驱动适应性免疫系统。
