美国约翰霍普金斯大学Andrew P. Lane和Mengfei Chen研究组合作发现，慢性炎症指导嗅觉干细胞功能从神经再生转向免疫防御。相关论文于2019年9月12日在线发表于《细胞—干细胞》。

研究人员发现，虽然炎症最初损害嗅觉神经元并激活水平基底干细胞（HBC）介导的再生，但持续的炎症将HBC锁定在未分化状态。小鼠HBC中的全基因表达揭示了NF-κB调节的细胞因子和趋化因子（包括CCL19，CCL20和CXCL10）的广泛上调，并伴随着“干性”相关转录因子的增强。功能缺陷研究确定了HBC在扩增炎症信号传导中是依赖于NF-κB的，导致巨噬细胞和T细胞局部增殖。慢性激活的HBC传递信号给巨噬细胞来维持免疫防御并防止Treg发生。在患病的人类嗅觉组织中，P63 +未分化状态下的活化HBC同样通过趋化因子产生促成炎症。这些结果结果建立了慢性鼻-鼻窦炎相关嗅觉丧失的机制，这是由神经上皮干细胞从再生到免疫防御的功能性转换引起的。

研究人员介绍，尽管嗅粘膜具有长寿命的HBC和显著的再生能力，但人嗅神经上皮的功能在慢性炎性鼻-鼻窦炎中显著受损。

附：英文原文

Title: Chronic Inflammation Directs an Olfactory Stem Cell Functional Switch from Neuroregeneration to Immune Defense

Author: Mengfei Chen, Randall R. Reed, Andrew P. Lane

Issue&Volume: 12 September 2019

Summary: 

Although olfactory mucosa possesses long-lived horizontal basal stem cells (HBCs) and remarkable regenerative capacity, the function of human olfactory neuroepithelium is significantly impaired in chronic inflammatory rhinosinusitis. Here, we show that, while inflammation initially damages olfactory neurons and activates HBC-mediated regeneration, continued inflammation locks HBCs in an undifferentiated state. Global gene expression in mouse HBCs reveals broad upregulation of NF-κB-regulated cytokines and chemokines including CCL19, CCL20, and CXCL10, accompanied by enhancement of “stemness”-related transcription factors. Loss-of-function studies identify an NF-κB-dependent role of HBCs in amplifying inflammatory signaling, contributing to macrophage and T cell local proliferation. Chronically activated HBCs signal macrophages to maintain immune defense and prevent Treg development. In diseased human olfactory tissue, activated HBCs in a P63 + undifferentiated state similarly contribute to inflammation through chemokine production. These observations establish a mechanism of chronic rhinosinusitis-associated olfactory loss, caused by a functional switch of neuroepithelial stem cells from regeneration to immune defense.

DOI: 10.1016/j.stem.2019.08.011

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30346-7