López-Guisa Jesús M, Howsmon Rebecca, Munro Andrew, Blair Kendall M, Fisher Edward, Hermes Heidi, Zager Richard, Stevens Anne M
Department of Pediatrics; University of Washington; Seattle, WA USA.
Chimerism. 2011 Apr;2(2):42-9. doi: 10.4161/chim.2.2.16446.
Maternal microchimerism (MMc) can persist for years in a child, and has been implicated in the pathogenesis of chronic inflammatory autoimmune diseases. Chimeric cells may either contribute to disease by acting as immune targets or expand in response to signals of injury, inflammation or repair. We investigated the role of maternal cells in tissue injury in the absence of autoimmunity by quantifying MMc by quantitative PCR in acute and chronic models of renal injury: (1) reversible acute renal injury, inflammation and regeneration induced by rhabdomyolysis and (2) chronic injury leading to fibrosis after unilateral ureteral obstruction. We found that MMc is common in the mouse kidney. In mice congenic with their mothers neither acute nor chronic renal injury with fibrosis influenced the levels or prevalence of MMc. Maternal cells expressing MHC antigens not shared by offspring (H2(b/d)) were detected at lower levels in all groups of homozygous H2(b/b) or H2(d/d) offspring, with or without renal injury, suggesting that partial tolerance to low levels of alloantigens may regulate the homeostatic levels of maternal cells within tissues. Maternal cells homozygous for H2(b) were lost in H2(b/d) offspring only after acute renal failure, suggesting that an inflammatory stimulus led to loss of tolerance to homozygous maternal cells. The study suggests that elevated MMc previously found in association with human autoimmune diseases may not be a response to non-specific injury or inflammatory signals, but rather a primary event integral to the pathogenesis of autoimmunity.
母源微嵌合体（MMc）可在儿童体内持续存在数年，并与慢性炎症性自身免疫性疾病的发病机制有关。嵌合细胞可能通过作为免疫靶点促成疾病，或者响应损伤、炎症或修复信号而增殖。我们通过在急性和慢性肾损伤模型中采用定量PCR定量MMc，研究了在无自身免疫情况下母源细胞在组织损伤中的作用：（1）横纹肌溶解诱导的可逆性急性肾损伤、炎症和再生，以及（2）单侧输尿管梗阻后导致纤维化的慢性损伤。我们发现MMc在小鼠肾脏中很常见。在与其母亲基因相同的小鼠中，急性或慢性肾损伤伴纤维化均未影响MMc的水平或发生率。在所有纯合H2（b/b）或H2（d/d）后代组中，无论有无肾损伤，表达后代所不共有的MHC抗原（H2（b/d））的母源细胞检测水平较低，这表明对低水平同种异体抗原的部分耐受性可能调节组织内母源细胞的稳态水平。仅在急性肾衰竭后，H2（b/d）后代中H2（b）纯合的母源细胞才会消失，这表明炎症刺激导致对纯合母源细胞的耐受性丧失。该研究表明，先前发现的与人类自身免疫性疾病相关的MMc升高可能不是对非特异性损伤或炎症信号的反应，而是自身免疫发病机制中不可或缺的原发性事件。
