Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, 90033-9080, CA, USA.
Division of Nephrology, Regional Hospital Lugano, Lugano, 6900, Switzerland.
Nat Commun. 2019 Mar 11;10(1):1157. doi: 10.1038/s41467-019-09092-2.
The mechanisms initiating late immune responses to an allograft are poorly understood. Here we show, via transcriptome analysis of serial protocol biopsies from kidney transplants, that the initial responses to kidney injury correlate with a late B lymphocyte signature relating to renal dysfunction and fibrosis. With a potential link between dysfunctional repair and immunoreactivity, we investigate the immunological consequences of dysfunctional repair examining chronic disease in mouse kidneys 18 months after a bilateral ischemia/reperfusion injury event. In the absence of foreign antigens, a sustained immune response involving both innate and adaptive immune systems accompanies a transition to chronic kidney damage. At late stages, B lymphocytes exhibite an antigen-driven proliferation, selection and maturation into broadly-reacting antibody-secreting cells. These findings reveal a previously unappreciated role for dysfunctional tissue repair in local immunomodulation that may have particular relevance to transplant-associated immunobiology.
对于同种异体移植物晚期免疫反应的启动机制知之甚少。在这里，我们通过对肾移植连续协议活检的转录组分析表明，对肾损伤的初始反应与与肾功能障碍和纤维化相关的晚期 B 淋巴细胞特征相关。由于功能障碍性修复与免疫反应之间存在潜在联系，我们通过检查双侧缺血/再灌注损伤事件 18 个月后小鼠肾脏的慢性疾病，研究了功能障碍性修复的免疫学后果。在没有外来抗原的情况下，涉及固有和适应性免疫系统的持续免疫反应伴随着向慢性肾脏损伤的转变。在晚期，B 淋巴细胞表现出抗原驱动的增殖、选择和成熟为广泛反应的抗体分泌细胞。这些发现揭示了功能障碍性组织修复在局部免疫调节中的一个以前未被认识的作用，这可能与移植相关的免疫生物学有特殊的关系。
