Kitching A Richard, Turner Amanda L, Wilson Gabriella R A, Edgtton Kristy L, Tipping Peter G, Holdsworth Stephen R
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Rd, Clayton, VIC 3168, Australia.
J Am Soc Nephrol. 2004 Sep;15(9):2373-82. doi: 10.1097/01.ASN.0000138545.89960.3A.
IL-13 is produced by T helper 2 (Th2) cells, has a role in stimulating Th2-mediated injury, alters humoral responses, and may directly suppress macrophage and neutrophil function. In immune renal disease, the engagement of different effector mediator systems, including humoral and cell-mediated effectors, can result in glomerular injury. Experimental crescentic glomerulonephritis (known as autologous anti-glomerular basement membrane glomerulonephritis) induced by planting an antigen in glomeruli of mice is Th1 directed, delayed-type hypersensitivity (DTH)-like, and antibody independent. To test the hypothesis that, like the counterregulatory Th2 cytokines IL-4 and IL-10, endogenous IL-13 limits effector Th1 responses in glomerulonephritis, crescentic glomerulonephritis was induced in IL-13+/+ and IL-13-/- mice. Although IL-13-/- mice developed increased serum antigen-specific antibody levels, increased glomerular antibody deposition and enhanced switching to the Th1-associated IgG2a subclass, they developed a similar degree of crescentic glomerulonephritis, with similar glomerular T cell/macrophage numbers, renal impairment, and proteinuria. Antigen-specific dermal DTH and IFN-gamma production by antigen-stimulated splenocytes was unaltered. In immune complex (apoferritin-induced) glomerulonephritis, where renal injury is humorally mediated, IL-13-/- mice developed enhanced humoral immune responses and increased proteinuria, with increased IgG2a responses, a more peripheral distribution of immune complexes, but no alterations in leukocyte recruitment. These results demonstrate dissociation of IL-13's effects in antigen induced renal disease with little effect on cellular responses but suppressive effects on humoral effectors and switching to IgG2a. They indicate a role for IL-13 in limiting antibody-mediated renal injury, but not in regulating DTH-like cell-mediated responses in the kidney.
白细胞介素-13（IL-13）由辅助性T细胞2（Th2）产生，在刺激Th2介导的损伤中起作用，改变体液免疫反应，并可能直接抑制巨噬细胞和中性粒细胞的功能。在免疫性肾病中，包括体液和细胞介导效应物在内的不同效应介质系统的参与可导致肾小球损伤。通过在小鼠肾小球中植入抗原诱导的实验性新月体性肾小球肾炎（称为自体抗肾小球基底膜肾小球肾炎）是Th1介导的、迟发型超敏反应（DTH）样且不依赖抗体的。为了验证内源性IL-13是否像反调节性Th2细胞因子IL-4和IL-10一样限制肾小球肾炎中效应性Th1反应这一假设，在IL-13+/+和IL-13-/-小鼠中诱导了新月体性肾小球肾炎。尽管IL-13-/-小鼠血清中抗原特异性抗体水平升高、肾小球抗体沉积增加且向Th1相关的IgG2a亚类的转换增强，但它们发生的新月体性肾小球肾炎程度相似，肾小球T细胞/巨噬细胞数量、肾功能损害和蛋白尿情况相似。抗原刺激的脾细胞产生的抗原特异性皮肤DTH和干扰素-γ未发生改变。在免疫复合物（脱铁铁蛋白诱导）性肾小球肾炎中，肾损伤由体液介导，IL-13-/-小鼠体液免疫反应增强且蛋白尿增加，IgG2a反应增强，免疫复合物的外周分布增多，但白细胞募集未发生改变。这些结果表明，IL-13在抗原诱导的肾脏疾病中的作用存在解离，对细胞反应影响较小，但对体液效应物有抑制作用，并影响向IgG2a的转换。它们表明IL-13在限制抗体介导的肾损伤中起作用，但在调节肾脏中类似DTH的细胞介导反应中不起作用。
