潘尼斯电池
生物
节点2
克罗恩病
抗菌肽
ATG16L1
免疫学
Wnt信号通路
先天免疫系统
细胞生物学
微生物学
抗菌剂
小肠
免疫系统
遗传学
疾病
信号转导
自噬
内科学
细胞凋亡
医学
生物化学
作者
Maureen J. Koslowski,Julia Beisner,Eduard F. Stange,Jan Wehkamp
标识
DOI:10.1016/j.ijmm.2009.08.011
摘要
Paneth cells (PCs) are specialized epithelial cells predominantly found in the small intestinal crypts of Lieberkuehn. They produce different broad spectrum antimicrobial peptides most abundantly the alpha-defensins HD-5 and -6 (DEFA5 und DEFA6). Both these PC products show a specific reduction in small intestinal Crohn's disease (CD) - a form of inflammatory bowel disease (IBD). Their decrease is independent of current inflammation and an association with a NOD2 frameshift mutation has been demonstrated. More recently, another independent and even more frequent mechanism has been found which is linked to diminished levels of the Wnt pathway transcription factor TCF7L2 (also known as TCF4). Besides regulating the expression of HD-5 and HD-6 as TCF4 target genes, the Wnt pathway also orchestrates Paneth cell differentiation and maturation and controls stem cell maintenance in the small intestine. Besides NOD2 (which is predominantly expressed in PC) and ATG16L1 (inter alia important in the exocytosis of PC products), TCF4 is the third gene which is associated with small intestinal CD and Paneth cell antimicrobial function. Thus, Paneth cells seem to be key player emphazising a paramount importance of antimicrobial host defense in small intestinal CD pathogenesis.
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