Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
PLoS One. 2012;7(9):e42248. doi: 10.1371/journal.pone.0042248. Epub 2012 Sep 6.
Mouse angiogenin 4 (Ang4) has previously been described as a Paneth cell-derived antimicrobial peptide important in epithelial host defence in the small intestine. However, a source for Ang4 in the large intestine, which is devoid of Paneth cells, has not been defined.
METHODOLOGY/PRINCIPAL FINDINGS: Analysis was performed on Ang4 expression in colonic tissue by qPCR and immunohistochemistry following infection with the large intestine dwelling helminth parasite Trichuris muris. This demonstrated an increase in expression of the peptide following infection of resistant BALB/c mice. Further, histological analysis of colonic tissue revealed the cellular source of this Ang4 to be goblet cells. To elucidate the mechanism of Ang4 expression immunohistochemistry and qPCR for Ang4 was performed on colonic tissue from T. muris infected mouse mutants. Experiments comparing C3H/HeN and C3H/HeJ mice, which have a natural inactivating mutation of TLR4, revealed that Ang4 expression is TLR4 independent. Subsequent experiments with IL-13 and IL-4 receptor alpha deficient mice demonstrated that goblet cell expression of Ang4 is controlled either directly or indirectly by IL-13.
The cellular source of mouse Ang4 in the colon following T. muris infection is the goblet cell and expression is under the control of IL-13.
鼠血管生成素 4(Ang4)先前被描述为一种潘氏细胞衍生的抗菌肽,在小肠的上皮宿主防御中很重要。然而,在没有潘氏细胞的大肠中,Ang4 的来源尚未确定。
方法/主要发现:通过 qPCR 和免疫组织化学分析感染大肠寄生虫旋毛虫后结肠组织中的 Ang4 表达。这表明在抵抗性 BALB/c 小鼠感染后,该肽的表达增加。此外,对结肠组织的组织学分析表明,这种 Ang4 的细胞来源是杯状细胞。为了阐明 Ang4 表达的机制,对感染旋毛虫的小鼠突变体的结肠组织进行了 Ang4 的免疫组织化学和 qPCR 分析。比较 C3H/HeN 和 C3H/HeJ 小鼠(具有 TLR4 的天然失活突变)的实验表明,Ang4 的表达与 TLR4 无关。随后对 IL-13 和 IL-4 受体 alpha 缺陷小鼠进行的实验表明,杯状细胞 Ang4 的表达受 IL-13 的直接或间接控制。
在 T. muris 感染后,结肠中鼠 Ang4 的细胞来源是杯状细胞,其表达受 IL-13 的控制。