Altered Th1/Th2 commitment contributes to lung senescence in CXCR3-deficient mice
Altered Th1/Th2 commitment contributes to lung senescence in CXCR3-deficient mice
复制标题
Th1/Th2 承诺的改变导致 CXCR3 缺陷小鼠的肺衰老
DOI：
10.1016/j.exger.2013.04.001
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发表时间：
2013-08-01
影响因子：
3.9
通讯作者：
Huang, Kewu
中科院分区：
文献类型：
--
作者：
Huang, Junmin;Li, Zongli;Huang, Kewu
衰老是与免疫失衡相关的不可避免的过程，其特征是包括肺在内的主要器官的功能进行性下降。然而，改变Th 1/Th 2承诺对肺衰老的影响在很大程度上是未知的。为了研究Th 1/Th 2平衡改变对肺老化的影响，我们测量了2月龄和20月龄CXCR 3缺陷（CXCR 3（-/-））C57 BL/6 J小鼠与野生型（WT）小鼠相比，Th 1和Th 2细胞的比例以及细胞因子、趋化因子、胶原沉积和其他相关生理和病理参数的表达。与相同年龄的WT组相比，在20个月CXCR 3（-/-）小鼠中观察到显著的体重减轻。尽管两组的肺功能和结构随年龄变化，但20-mo CXCR 3（-/-）小鼠的中心气道阻力（Rn）、组织弹性（H）和阻尼（G）均显著低于WT小鼠。相反，20个月CXCR 3（-/-）小鼠的全肺体积（V-L）、肺泡平均线性截距长度（L-m）和肺总胶原含量显著升高。随着年龄的增长，WT小鼠的肺具有典型的Th 1型状态（Th 1细胞数量和细胞因子IFN-γ和CXCR 3配体浓度增加），而CXCR 3（-/-）小鼠显示出Th 2型极化（Th 1细胞比例和CXCR 3配体浓度降低，但IL-4水平升高）。我们的数据表明，免疫衰老与肺衰老有关，改变Th 1/Th 2失衡有利于CXCR 3（-/-）小鼠的Th 2优势，这有助于在该模型中加速肺衰老的过程。(C)2013 Elsevier Inc. All rights reserved.
Aging is an inevitable process associated with immune imbalance, which is characterized by a progressive functional decline in major organs, including lung. However, effects of altered Th1/Th2 commitment on lung senescence are largely unknown. To examine effects of altered Th1/Th2 balance on lung aging, we measured proportions of Th1 and Th2 cells and expression of cytokines, chemokines, collagen deposition and other relevant physiological and pathological parameters in 2- and 20-months-old (mo) CXCR3-deficient (CXCR3(-/-)) C57BL/6J mice compared with wild-type (WT) mice. There was a significant weight-loss observed in 20-mo CXCR3(-/-) mice compared with the same aged WT group. Although lung function and structure changed with age in both groups, central airway resistance (Rn), tissue elastance (H) and damping (G) were significantly lower in 20-mo CXCR3(-/-) mice than those of WT mice. In contrast, the whole lung volume (V-L), the mean linear intercept length of alveolar (L-m), and the total lung collagen content were significantly elevated in 20-mo CXCR3(-/-) mice. With aging, the lungs of WT mice had typical Th1-type status (increased population of Th1 cells and concentrations of cytokine IFN-gamma and CXCR3 ligands) while CXCR3(-/-) mice showed Th2-type polarization (decreased proportion of Th1 cells and concentrations of CXCR3 ligands but increased level of IL-4). Our data suggest that Immunosenescence is associated with lung aging, and that altered Th1/Th2 imbalance favors Th2 predominance in CXCR3(-/-) mice, which contributes to the process of accelerated lung aging in this model. (C) 2013 Elsevier Inc. All rights reserved.