The absence of interleukin 10 affects the morphology, differentiation, granule content and the production of cryptidin-4 in Paneth cells in mice
The absence of interleukin 10 affects the morphology, differentiation, granule content and the production of cryptidin-4 in Paneth cells in mice
复制标题
DOI：
10.1371/journal.pone.0221618
复制
发表时间：
2019-09-11
期刊：
影响因子：
3.7
通讯作者：
Bueno, Susan M.
中科院分区：
文献类型：
--
作者：
Berkowitz, Loni;Pardo-Roa, Catalina;Bueno, Susan M.
潘氏细胞（Paneth cell，PC）是小肠的特化上皮细胞，含有大量分泌颗粒，颗粒内含有抗菌肽和营养因子，对控制微生物生长和维持肠道完整性至关重要。其功能的改变与正常微生物群的失衡、胃肠道感染和炎症过程（如克罗恩病（CD））相关。用于研究CD的最常见的鼠模型之一是IL-10（-/-）小鼠。IL-10（-/-）小鼠在常规条件下饲养并与肠道微生物接触时发生由Th 1免疫应答介导的急性小肠结肠炎。尽管PC功能的改变与CD相关，但尚未在该小鼠模型中对其进行表征。我们发现在特定的无病原体条件下，IL-10（-/-）小鼠在发生肠道炎症之前，在IL-10（-/-）小鼠回肠中的隐窝底部具有异常颗粒和大量未成熟的PC，沿着印度刺猬蛋白的表达减少。此外，IL-10（-/-）Paneth细胞表现出隐肽-4的表达减少，以及溶菌酶+颗粒的不均匀分布。在常规微生物群定植后，地穴底部PC成熟的变化并未改变。另一方面，微生物群的消耗改变了表型，但没有使PC正常化。我们的研究结果表明，IL-10可能是必要的PC的完整性。此外，我们的研究结果有助于解释为什么IL-10（-/-）小鼠对微生物的反应会发生小肠结肠炎。
Paneth cells (PCs) are specialized epithelial cells of the small bowel that contain multiple secretory granules filled with antimicrobial peptides and trophic factors, which are essential for the control of the microorganisms growth and maintaining intestinal integrity. Alterations in their function are associated with an imbalance of the normal microbiota, gastrointestinal infections and inflammatory processes, such as Crohn's disease (CD). One of the most common murine models for studying CD is IL-10(-/-) mouse. IL-10(-/-) mice when housed in conventional conditions and take contact with commensal microorganisms develop an acute enterocolitis mediated by a Th1 immune response. Even though, alterations in PCs function are related to CD, they had not been characterized yet in this mouse model. Here we show that in specific pathogen free conditions IL-10(-/-) mice have aberrant granules and a large number of immature PCs at the bottom of the crypt in the ileum of IL-10(-/-) mice before developing intestinal inflammation, along with a reduced expression of Indian Hedgehog. In addition, IL-10(-/-) Paneth cells presented a reduced expression of cryptidin-4, and a heterogeneous distribution of lysozyme+ granules. The alterations in the maturation of the PCs at the bottom of the crypt were not modified after the colonization by the conventional microbiota. On the other hand, depletion of microbiota altered the phenotype, but did not normalize PCs. Our results suggest that IL-10 could be necessary for the integrity of PCs. Moreover, our results help to explain why IL-10(-/-) mice develop enterocolitis in response to microorganisms.