Department of Neuropathology, Weatherall Institute of Molecular Medicine, Oxford Radcliffe NHS Trust, Oxford, United Kingdom.
Am J Pathol. 2011 Feb;178(2):794-802. doi: 10.1016/j.ajpath.2010.10.043.
IL-17-producing CD4(+) T cells (Th-17) contribute to the pathogenesis of experimental autoimmune encephalomyelitis and are associated with active disease in multiple sclerosis (MS). In addition to IL-17, Th-17 cells can also express IL-21, IL-22, and IL-6 under Th-17-polarizing conditions (IL-6 and transforming growth factor-β). In this study we investigated IL-21 and IL-21 receptor (IL-21R) expression in MS lesions by in situ hybridization and immunohistochemistry. We detected strongly IL-21(+) infiltrating cells predominantly in acute but also in chronic active white matter MS lesions in which IL-21 expression was restricted to CD4(+) cells. In contrast, IL-21R was much more broadly distributed on CD4(+), CD19(+), and CD8(+) lymphocytes but not major histocompatibility complex class-II(+) macrophages/microglia. Interestingly, in cortical areas we detected both IL-21 and IL-21R expression by neurons. These findings suggest role(s) for IL-21 in both the acute and chronic stages of MS via direct effects on T and B lymphocytes and, demonstrated for the first time, also on neurons.
IL-17 产生的 CD4(+) T 细胞（Th-17）有助于实验性自身免疫性脑脊髓炎的发病机制，并与多发性硬化症（MS）的活跃疾病相关。除了 IL-17，Th-17 细胞在 Th-17 极化条件下（IL-6 和转化生长因子-β）也可以表达 IL-21、IL-22 和 IL-6。在这项研究中，我们通过原位杂交和免疫组织化学检测了 MS 病变中 IL-21 和 IL-21 受体（IL-21R）的表达。我们检测到强烈的 IL-21(+)浸润细胞主要存在于急性但也存在于慢性活动的白质 MS 病变中，其中 IL-21 表达仅限于 CD4(+)细胞。相比之下，IL-21R 更广泛地分布在 CD4(+)、CD19(+)和 CD8(+)淋巴细胞上，但不分布在主要组织相容性复合体 II(+)巨噬细胞/小胶质细胞上。有趣的是，在皮质区域，我们检测到神经元表达 IL-21 和 IL-21R。这些发现表明 IL-21 在 MS 的急性和慢性阶段都发挥作用，通过直接作用于 T 和 B 淋巴细胞，并且首次证明还作用于神经元。
