Aging in the absence of TLR2 is associated with reduced IFN-γ responses in the large intestine and increased severity of induced colitis
Aging in the absence of TLR2 is associated with reduced IFN-γ responses in the large intestine and increased severity of induced colitis
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DOI：
10.1189/jlb.0807557
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发表时间：
2008-04-01
影响因子：
5.5
通讯作者：
Marshall, Jean S.
中科院分区：
文献类型：
--
作者：
Albert, Eric J.;Marshall, Jean S.
肠道炎性反应相关的免疫功能变化及其对肠道炎症的影响知之甚少。先天免疫缺陷已被证明会增强肠道炎症，并已在衰老时得到证实。本研究旨在确定在存在和不存在TLR 2的情况下衰老对肠道炎症的影响。检查年轻和老年（> 60周）、对照C57 B1/6和TLR 2缺陷（TLR 2（-/-））小鼠。在基线或用葡聚糖硫酸钠（DSS）治疗5天和5天或13天恢复后，分析盲肠和中结肠的组织损伤、细胞因子谱和三叶因子3（TFF 3）表达。未经治疗的老年TLR 2（-/-）小鼠没有明显的肠道炎症，但与年轻小鼠相比，结肠IFN-γ和IL-10减少。老年TLR 2（-/-）小鼠比其他组发生更严重的结肠炎，如组织学检查和总体体重减轻所示。DSS治疗后，年轻小鼠的结肠IFN-γ显著增加，但老年小鼠则无。DSS处理后，老年但非年轻TLR 2（-/-）小鼠的盲肠中的TFF 3显著减少，结肠中的TFF 3显著增加。这些结果表明，即使在衰老时，TLR 2缺陷动物也不会发生肠道疾病。然而，它们未能对炎症性损伤做出适当的反应，其后果在老年动物中最为严重。与衰老相关的细胞因子和TFF 3变化可能导致更严重的肠道炎症。
Age-associated changes in immune function and their implications for intestinal inflammation are poorly understood. Defects in innate immunity have been shown to enhance intestinal inflammation and have been demonstrated upon aging. This study aimed to determine the consequences of aging in the presence and absence of TLR2 on intestinal inflammation. Young and aged (> 60 weeks), control C57Bl/6 and TLR2-deficient (TLR2(-/-)) mice were examined. The cecum and mid-colon were analyzed for tissue damage, cytokine profiles, and trefoil factor 3 (TFF3) expression at baseline or after 5 days of treatment with dextran sodium sulfate (DSS) and 5 or 13 days recovery. Untreated, aged TLR2(-/-) mice had no significant intestinal inflammation but had reduced colonic IFN-gamma and IL-10 compared with younger mice. Aged TLR2(-/-) mice developed more severe colitis than other groups, as indicated by histological examination and overall weight loss. There were significant increases in colonic IFN-gamma following DSS treatment in young but not in aged mice. TFF3 was substantially reduced in the cecum and increased in the colon of aged but not younger TLR2(-/-) mice following DSS treatment. These results demonstrate that even upon aging, TLR2-deficient animals did not develop intestinal disease. However, they failed to respond appropriately to an inflammatory insult, and the consequences of this were most severe in aged animals. Cytokine and TFF3 changes associated with aging may contribute to more severe intestinal inflammation.