Yang Hua, Madison Blair, Gumucio Deborah L, Teitelbaum Daniel H
Dept. of General Surgery, Xinqiao Hospital, Third Military Medical Univ., Chongqing 400037, China.
Am J Physiol Gastrointest Liver Physiol. 2008 Jun;294(6):G1421-30. doi: 10.1152/ajpgi.00060.2008. Epub 2008 Apr 10.
IL-7 plays a crucial role in controlling T cell development and homeostasis. Since IL-7 may be derived from extraintestinal sources, and exogenous IL-7 broadly affects lymphoid populations, the actions of epithelial cell (EC)-derived IL-7 are not fully understood. The effect of intestinal specific expression of IL-7 on intestinal mucosal lymphocytes was investigated by using an IL-7 transgenic mouse model. We generated an intestinal EC-specific overexpressing IL-7 transgenic mouse model (IL-7(vill)) and compared their phenotype and function to wild-type C57BL/6J mice. EC-derived IL-7 overexpression was found to be exclusively in the small and large intestine. Numbers and subtypes of mucosal lymphocytes, including intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL), significantly changed in IL-7(vill) mice. From a functional standpoint, IEL proliferation also significantly increased in IL-7(vill) mice. IEL cytokine expression significantly changed in both T cell receptor (TCR)-alphabeta(+) and TCR-gammadelta(+) IEL subpopulations, including a significant increase in IFN-gamma and TNF-alpha as well as an increase in keratinocyte growth factor expression. EC expression of CD103 (integrin alpha(E)beta(7)), the ligand of E-cadherin, markedly upregulated and may account for a mechanism of the massive expansion of IEL in transgenic mice. Systemic lymphoid populations did not change in transgenic mice. IL-7 overexpression by intestinal EC significantly affected IEL phenotype and function. These results offer insight into the role of IL-7 in IEL development and suggest a critical role of EC-derived expression of IL-7 in the phenotype and function of IEL.
白细胞介素-7（IL-7）在控制T细胞发育和内环境稳定方面发挥着关键作用。由于IL-7可能来源于肠道外，且外源性IL-7广泛影响淋巴细胞群体，上皮细胞（EC）来源的IL-7的作用尚未完全明确。通过使用IL-7转基因小鼠模型，研究了肠道特异性表达IL-7对肠道黏膜淋巴细胞的影响。我们构建了一种肠道EC特异性过表达IL-7的转基因小鼠模型（IL-7(vill)），并将其表型和功能与野生型C57BL/6J小鼠进行比较。发现EC来源的IL-7过表达仅存在于小肠和大肠。在IL-7(vill)小鼠中，包括上皮内淋巴细胞（IEL）和固有层淋巴细胞（LPL）在内的黏膜淋巴细胞数量和亚型发生了显著变化。从功能角度来看，IL-7(vill)小鼠中IEL增殖也显著增加。IEL细胞因子表达在T细胞受体（TCR）-αβ(+)和TCR-γδ(+) IEL亚群中均发生显著变化，包括IFN-γ和TNF-α显著增加以及角质形成细胞生长因子表达增加。E-钙黏蛋白的配体CD103（整合素α(E)β(7)）在EC中的表达明显上调，这可能解释了转基因小鼠中IEL大量扩增的机制。转基因小鼠的全身淋巴细胞群体没有变化。肠道EC过表达IL-7显著影响IEL表型和功能。这些结果为IL-7在IEL发育中的作用提供了见解，并表明EC来源的IL-7表达在IEL表型和功能中起关键作用。
