miR-125b inhibits goblet cell differentiation in allergic airway inflammation by targeting SPDEF

2016 ◽  
Vol 782 ◽  
pp. 14-20 ◽  
Author(s):  
Zhaoe Liu ◽  
Xing Chen ◽  
Qiaoling Wu ◽  
Jia Song ◽  
Lijun Wang ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Airway Inflammation ◽  
Goblet Cell ◽  
Allergic Airway Inflammation ◽  
Goblet Cell Differentiation

Goblet Cell Hyperplasia is not Epithelial-Autonomous in the Cftr Knockout Intestine

2021 ◽  
Author(s):  
Nancy M Walker ◽  
Jinghua Liu ◽  
Sarah M Young ◽  
Rowena A Woode ◽  
Lane L. Clarke
Keyword(s):  
Cell Differentiation ◽  
Goblet Cell ◽  
Ex Vivo ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia ◽  
Cell Numbers ◽  
Markers Of Inflammation ◽  
Tlr4 Agonist ◽  
Goblet Cell Differentiation ◽  
Mucosal Morphology

Goblet cell hyperplasia is an important manifestation of cystic fibrosis (CF) disease in epithelial-lined organs. Explants of CF airway epithelium show normalization of goblet cell numbers; therefore we hypothesized that small intestinal enteroids from Cftr knockout (KO) mice would not exhibit goblet cell hyperplasia. Toll-like receptors 2 and 4 (Tlr2, Tlr4) were investigated as markers of inflammation and influence on goblet cell differentiation. Ex vivo studies found goblet cell hyperplasia in Cftr KO jejunum as compared to wild-type (WT). IL-13, SAM pointed domain-containing ETS transcription factor (Spdef), Tlr2 and Tlr4 protein expression was increased in Cftr KO intestine relative to WT. In contrast, WT and Cftr KO enteroids did not exhibit differences in basal or IL-13-stimulated goblet cell numbers, or differences in expression of Tlr2, Tlr4 and Spdef. Ileal goblet cell numbers in Cftr KO/Tlr4 KO and Cftr KO/Tlr2 KO mice were not different from Cftr KO mice, but enumeration was confounded by altered mucosal morphology. Treatment with Tlr4 agonist LPS did not affect goblet cell numbers in WT or Cftr KO enteroids, whereas the Tlr2 agonist Pam3Csk4 stimulated goblet cell hyperplasia in both genotypes. Pam3Csk4 stimulation of goblet cell numbers was associated with suppression of Notch1 and Neurog3 expression and upregulated determinants of goblet cell differentiation. We conclude that goblet cell hyperplasia and inflammation of the Cftr KO small intestine are not exhibited by enteroids, indicating that this manifestation of CF intestinal disease is not epithelial-automatous but secondary to the altered CF intestinal environment.

scholarly journals IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation

2018 ◽  
Vol 49 (1) ◽  
pp. 66-78 ◽  
Author(s):  
Diana C. Yánez ◽  
Hemant Sahni ◽  
Susan Ross ◽  
Anisha Solanki ◽  
Ching-In Lau ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper

scholarly journals IL-33 Induces Murine Intestinal Goblet Cell Differentiation Indirectly via Innate Lymphoid Cell IL-13 Secretion

2018 ◽  
Vol 202 (2) ◽  
pp. 598-607 ◽  
Author(s):  
Amanda Waddell ◽  
Jefferson E. Vallance ◽  
Amy Hummel ◽  
Theresa Alenghat ◽  
Michael J. Rosen
Keyword(s):  
Cell Differentiation ◽  
Goblet Cell ◽  
Lymphoid Cell ◽  
Innate Lymphoid Cell ◽  
Goblet Cell Differentiation

scholarly journals P105 Glutathione S-transferase theta 1 protects against colitis through goblet cell differentiation via interleukin-22

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S188-S188
Author(s):  
J H Kim ◽  
J B Ahn ◽  
D H Kim ◽  
S Kim ◽  
H W Ma ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Immune Responses ◽  
Goblet Cell ◽  
Goblet Cells ◽  
Dependent Manner ◽  
Glutathione S Transferase ◽  
Host Immune Responses ◽  
Interleukin 22 ◽  
Gstt1 Gene ◽  
Goblet Cell Differentiation

Abstract Background The enzyme glutathione S-transferase theta 1 (GSTT1) is involved in detoxifying chemicals, including reactive oxygen species (ROS). Oxidative stress plays a key role in the pathogenesis of inflammatory bowel disease (IBD). Although mutation of the GSTT1 gene increases IBD susceptibility, the underlying mechanisms remain unexplained. Methods The Gstt1 gene was intrarectally or intraperitoneally delivered to mice with dextran sodium sulphate (DSS)-induced colitis. The GSTT1 gene was knocked down or knocked out using short interfering RNA or genome editing, respectively. Protein and mRNA expression and differentiation of goblet cells were evaluated. Results We identified decreased expression of GSTT1 in inflamed tissues from IBD patients and mice compared with their control counterparts, respectively. We also noted attenuation of colitis through gene transfer of Gstt1 to DSS-treated mice via the interleukin-22 (IL-22) pathway. GSTT1 was differently regulated by pathogens and host immune responses. Down-regulation of GSTT1 reduced innate defence responses and goblet cell differentiation. The GSTT1 mutation in intestinal epithelial cells as well as IBD patients diminished its dimerisation, which was connected to insufficient phosphorylation of signal transducer and activator of transcription 3 and p38/mitogen-activated protein kinase by their common activator, IL-22. Conclusion GSTT1 ameliorated IL-22 in colitis in a dependent manner and contributed as a modulator of goblet cells through sensing pathogens and host immune responses. Its mutations are linked to chronic intestinal inflammation due to its insufficient dimerisation. Our results provide new insights into GSTT1 mutations and their functional consequences in IBDs.

scholarly journals WNT/RYK signaling restricts goblet cell differentiation during lung development and repair

2019 ◽  
Vol 116 (51) ◽  
pp. 25697-25706 ◽  
Author(s):  
Hyun-Taek Kim ◽  
Wenguang Yin ◽  
Yuko Nakamichi ◽  
Paolo Panza ◽  
Beate Grohmann ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cells ◽  
Goblet Cell ◽  
Lung Development ◽  
Alveolar Epithelial Cells ◽  
Airway Epithelial ◽  
Cell Hyperplasia ◽  
Mucus Hypersecretion ◽  
Goblet Cell Hyperplasia ◽  
Goblet Cell Differentiation

Goblet cell metaplasia and mucus hypersecretion are observed in many pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the regulation of goblet cell differentiation remains unclear. Here, we identify a regulator of this process in anN-ethyl-N-nitrosourea (ENU) screen for modulators of postnatal lung development;Rykmutant mice exhibit lung inflammation, goblet cell hyperplasia, and mucus hypersecretion. RYK functions as a WNT coreceptor, and, in the developing lung, we observed high RYK expression in airway epithelial cells and moderate expression in mesenchymal cells as well as in alveolar epithelial cells. From transcriptomic analyses and follow-up studies, we found decreased WNT/β-catenin signaling activity in the mutant lung epithelium. Epithelial-specificRykdeletion causes goblet cell hyperplasia and mucus hypersecretion but not inflammation, while club cell-specificRykdeletion in adult stages leads to goblet cell hyperplasia and mucus hypersecretion during regeneration. We also found that the airway epithelium of COPD patients often displays goblet cell metaplastic foci, as well as reduced RYK expression. Altogether, our findings reveal that RYK plays important roles in maintaining the balance between airway epithelial cell populations during development and repair, and that defects in RYK expression or function may contribute to the pathogenesis of human lung diseases.

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