scholarly journals In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche

Nature ◽  
2011 ◽  
Vol 474 (7350) ◽  
pp. 216-219 ◽  
Author(s):  
Joji Fujisaki ◽  
Juwell Wu ◽  
Alicia L. Carlson ◽  
Lev Silberstein ◽  
Prabhakar Putheti ◽  
...  
2019 ◽  
Vol 17 ◽  
pp. 100244 ◽  
Author(s):  
Gloria Allocca ◽  
Russell Hughes ◽  
Ning Wang ◽  
Hannah K Brown ◽  
Penelope D Ottewell ◽  
...  

2013 ◽  
Vol 41 (8) ◽  
pp. S31
Author(s):  
Ingo Roeder ◽  
Axel Krinner ◽  
Nico Scherf ◽  
Marc Scott ◽  
Narges Rashidi ◽  
...  

2016 ◽  
Vol 179 (4) ◽  
pp. 669-673 ◽  
Author(s):  
Ilaria M. Michelozzi ◽  
Alice Pievani ◽  
Fabio Pagni ◽  
Laura Antolini ◽  
Marta Verna ◽  
...  

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S7-S8
Author(s):  
Safina Gadeock ◽  
Cambrian Liu ◽  
Brent Polk

Abstract Tumor necrosis factor (TNF) is a highly expressed cytokine in inflammatory bowel disease (IBD). Although TNF can induce colonic epithelial dysfunction and apoptosis, recent studies suggest that TNF signalling promotes epithelial wound repair and stem cell function. Here we investigated the role of TNF receptor 1 (TNFR1) in mediating TNF’s effects on colonic epithelial stem cells, integral to mucosal healing in colitis. We demonstrate that Tnfr1-/- mice exhibit loss in Lgr5 expression (-52%, p<0.02; N=6) compared to wildtype (WT) controls. However, the opposite result was found in vitro, wherein murine Tnfr1-/- colonoids demonstrated a significant increase in Lgr5 expression (66%, p<0.007; N=6) compared to WT colonoids. Similarly, human colonoids treated with an anti-TNFR1 antibody also demonstrated an increase in Lgr5 expression, relative to IgG controls. To resolve the contradiction in the in vivo versus in vitro environment, we hypothesized that mesenchymal TNFR1 expression regulates the epithelial stem cell niche. To determine the relationships between these cell types, we co-cultured WT or Tnfr1-/- colonoids with WT or Tnfr1-/- colonic myofibroblasts (CMFs). We found that epithelial Lgr5 expression was significantly higher (by 52%, p<0.05; N=3) when co-cultured with WT compared to TNFR1-/- myofibroblasts. The loss of TNFR1 expression in vivo increases the number of αSMA+ mesenchymal cells by nearly 56% (N=6) but considerably reduces the pericryptal PDGFRα+ cells, suggesting modifications in mesenchymal populations that contribute to the epithelial stem cell niche. Functionally, primary Tnfr1-/--CMFs displayed PI3k (p<0.001; N=3) and MAPK (p<0.01; N=3)-dependent increases in migration, proliferation, and differentiation, but RNA profiling demonstrated by diminished levels of stem cell niche factors, Rspo3 (-80%, p<0.0001; N=6) and Wnt2b (-63%, p<0.008; N=6) compared to WT-CMFs. Supplementation with 50ng recombinant Rspo3 for 5 d to Lgr5-GFP organoids co-cultured with TNFR1-/--CMFs restored Lgr5 expression to wildtype levels. Therefore, TNFR1-mediated TNF signalling in mesenchymal cells promotes their ability to support an epithelial stem cell niche. These results should motivate future studies of the stem cell niche in the context of long-term treatment with anti-TNF therapies.


2019 ◽  
Vol 38 (19) ◽  
Author(s):  
Daniel Peña‐Jimenez ◽  
Silvia Fontenete ◽  
Diego Megias ◽  
Coral Fustero‐Torre ◽  
Osvaldo Graña‐Castro ◽  
...  

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