Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, AmadeoLab, Fondazione IRCCS Istituto Nazionale Tumori, via Amadeo 42, 20133 Milan, Italy.
J Autoimmun. 2011 Dec;37(4):300-10. doi: 10.1016/j.jaut.2011.09.002. Epub 2011 Sep 29.
Lymphnode swelling during immune responses is a transient, finely regulated tissue rearrangement, accomplished with the participation of the extracellular matrix. Here we show that murine and human reactive lymph nodes express SPARC in the germinal centres. Defective follicular dendritic cell networking in SPARC-deficient mice is accompanied by a severe delay in the arrangement of germinal centres and development of humoral autoimmunity, events that are linked to Th17 development. SPARC is required for the optimal and rapid differentiation of Th17 cells, accordingly we show delayed development of experimental autoimmune encephalomyelitis whose pathogenesis involves Th17. Not only host radioresistant cells, namely follicular dendritic cells, but also CD4(+) cells are the relevant sources of SPARC, in vivo. Th17 differentiation and germinal centre formation mutually depend on SPARC for a proper functional crosstalk. Indeed, Th17 cells can enter the germinal centres in SPARC-competent, but not SPARC-deficient, mice. In summary, SPARC optimizes the changes occurring in lymphoid extracellular matrix harboring complex interactions between follicular dendritic cells, B cells and Th17 cells.
在免疫反应过程中，淋巴结肿胀是一种短暂的、精细调节的组织重排，这一过程伴随着细胞外基质的参与。在这里，我们发现鼠类和人类反应性淋巴结在生发中心表达 SPARC。在 SPARC 缺陷型小鼠中，滤泡树突状细胞网络的缺陷伴随着生发中心排列和体液自身免疫发展的严重延迟，这些事件与 Th17 细胞的发展有关。SPARC 是 Th17 细胞最佳和快速分化所必需的，因此我们发现实验性自身免疫性脑脊髓炎的发展延迟，其发病机制涉及 Th17 细胞。不仅宿主辐射抗性细胞，即滤泡树突状细胞，而且 CD4(+)细胞也是体内 SPARC 的相关来源。Th17 分化和生发中心形成相互依赖于 SPARC 进行适当的功能串扰。事实上，Th17 细胞可以进入 SPARC 功能正常但不缺乏 SPARC 的小鼠的生发中心。总之，SPARC 优化了淋巴样细胞外基质中发生的变化，其中滤泡树突状细胞、B 细胞和 Th17 细胞之间存在复杂的相互作用。
