Dysregulated Immune Responses by ASK1 Deficiency Alter Epithelial Progenitor Cell Fate and Accelerate Metaplasia Development during H. pylori Infection.
Dysregulated Immune Responses by ASK1 Deficiency Alter Epithelial Progenitor Cell Fate and Accelerate Metaplasia Development during H. pylori Infection.
复制标题
DOI：
10.3390/microorganisms8121995
复制
发表时间：
2020-12-14
期刊：
影响因子：
4.5
通讯作者：
Koike K
中科院分区：
文献类型：
--
作者：
Hayakawa Y;Hirata Y;Hata M;Tsuboi M;Oya Y;Kurokawa K;Abe S;Arai J;Suzuki N;Nakagawa H;Fujiwara H;Tateishi K;Maeda S;Koike K
对H.幽门引起的萎缩和化生尚未完全了解。在这里，我们证明了凋亡信号调节激酶1（ASK 1）和下游MAPK作为宿主免疫反应和上皮细胞对H。幽门感染ASK 1基因缺陷导致炎症增强，大量炎性细胞包括Gr-1+ CD 11b+髓源性抑制细胞（MDSC）募集到受感染的胃中。凋亡巨噬细胞释放IL-1β的增加和TH-1极化免疫反应的增强导致ASK 1基因敲除小鼠上皮细胞中STAT 1和NF-κB活化。ASK 1基因敲除小鼠中免疫和上皮活化失调导致胃祖细胞急剧扩增和大量化生发展。骨髓移植实验表明，炎症细胞中的ASK 1对于诱导免疫紊乱和上皮化生变化至关重要，而上皮细胞中的ASK 1调节干/祖细胞区的细胞增殖而不改变炎症和分化。这些结果表明，H.幽门螺杆菌诱导的免疫细胞可通过ASK 1信号传导调节上皮内稳态和作为炎性小生境的细胞命运。
The mechanism of H. pylori-induced atrophy and metaplasia has not been fully understood. Here, we demonstrate the novel role of Apoptosis signal-regulating kinase 1 (ASK1) and downstream MAPKs as a regulator of host immune responses and epithelial maintenance against H. pylori infection. ASK1 gene deficiency resulted in enhanced inflammation with numerous inflammatory cells including Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) recruited into the infected stomach. Increase of IL-1β release from apoptotic macrophages and enhancement of TH1-polarized immune responses caused STAT1 and NF-κB activation in epithelial cells in ASK1 knockout mice. Dysregulated immune and epithelial activation in ASK1 knockout mice led to dramatic expansion of gastric progenitor cells and massive metaplasia development. Bone marrow transplantation experiments revealed that ASK1 in inflammatory cells is critical for inducing immune disorder and metaplastic changes in epithelium, while ASK1 in epithelial cells regulates cell proliferation in stem/progenitor zone without changes in inflammation and differentiation. These results suggest that H. pylori-induced immune cells may regulate epithelial homeostasis and cell fate as an inflammatory niche via ASK1 signaling.
登录
查看更多内容
影响因子：
16.6
作者：
Dubeykovskaya Z;Si Y;Chen X;Worthley DL;Renz BW;Urbanska AM;Hayakawa Y;Xu T;Westphalen CB;Dubeykovskiy A;Chen D;Friedman RA;Asfaha S;Nagar K;Tailor Y;Muthupalani S;Fox JG;Kitajewski J;Wang TC
通讯作者：
Wang TC
影响因子：
11.2
作者：
Cai, X;Stoicov, C;Houghton, JM
通讯作者：
Houghton, JM
影响因子：
29.4
作者：
Hata M;Kinoshita H;Hayakawa Y;Konishi M;Tsuboi M;Oya Y;Kurokawa K;Hayata Y;Nakagawa H;Tateishi K;Fujiwara H;Hirata Y;Worthley DL;Muranishi Y;Furukawa T;Kon S;Tomita H;Wang TC;Koike K
通讯作者：
Koike K
DOI：
10.1152/ajpgi.00187.2006
发表时间：
2006-12-01
影响因子：
4.5
作者：
Goldenring, James R.;Nomura, Sachiyo
通讯作者：
Nomura, Sachiyo
影响因子：
50.3
作者：
Hayakawa Y;Ariyama H;Stancikova J;Sakitani K;Asfaha S;Renz BW;Dubeykovskaya ZA;Shibata W;Wang H;Westphalen CB;Chen X;Takemoto Y;Kim W;Khurana SS;Tailor Y;Nagar K;Tomita H;Hara A;Sepulveda AR;Setlik W;Gershon MD;Saha S;Ding L;Shen Z;Fox JG;Friedman RA;Konieczny SF;Worthley DL;Korinek V;Wang TC
通讯作者：
Wang TC