scholarly journals TNFAIP8 Regulates Intestinal Epithelial Cell Differentiation and May Alter Terminal Differentiation of Secretory Progenitors

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 871
Author(s):  
Ryan Hood ◽  
Youhai H. Chen ◽  
Jason R. Goldsmith
Keyword(s):  
Cell Fate ◽  
Dynamic Environment ◽  
Terminal Differentiation ◽  
Intestinal Epithelial ◽  
Necrosis Factor Alpha ◽  
Cell Fate Decisions ◽  
Pi3k Activity ◽  
Tuft Cell ◽  
Undifferentiated State ◽  
Factor Alpha

The intestine is a highly proliferative dynamic environment that relies on constant self-renewal of the intestinal epithelium to maintain homeostasis. Tumor necrosis factor-alpha-induced protein 8 (TNFAIP8 or TIPE0) is a regulator of PI3K-mediated signaling. By binding to PIP2 and PIP3, TIPE family members locally activate PI3K activity while globally inhibiting PI3K activity through sequestration of membranous PIP2. Single-cell RNA sequencing survey of Tipe0−/− small intestine was used to investigate the role of TIPE0 in intestinal differentiation. Tipe0−/− intestinal cells were shown to shift towards an undifferentiated state, with the notable exception of goblet cells. Additionally, three possible novel regulators of terminal cell fate decisions in the secretory lineage were identified: Nupr1, Kdm4a, and Gatad1. We propose that these novel regulators drive changes involved in goblet cell (Nupr1) or tuft cell (Kdm4a and Gatad1) fate commitment and that TIPE0 may play a role in orchestrating terminal differentiation.

scholarly journals Temperature regulates NF-κB dynamics and function through timing of A20 transcription

2018 ◽  
Vol 115 (22) ◽  
pp. E5243-E5249 ◽  
Author(s):  
C. V. Harper ◽  
D. J. Woodcock ◽  
C. Lam ◽  
M. Garcia-Albornoz ◽  
A. Adamson ◽  
...  
Keyword(s):  
Cell Fate ◽  
Target Genes ◽  
Early Response ◽  
Strong Temperature Dependence ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Multidimensional Information ◽  
Dynamics And Function ◽  
And Function ◽  
Necrosis Factor

NF-κB signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-κB were affected by temperature within the mammalian physiological range (34 °C to 40 °C). An increase in temperature led to an increase in NF-κB nuclear/cytoplasmic oscillation frequency following Tumor Necrosis Factor alpha (TNFα) stimulation. Mathematical modeling suggested that this temperature sensitivity might be due to an A20-dependent mechanism, and A20 silencing removed the sensitivity to increased temperature. The timing of the early response of a key set of NF-κB target genes showed strong temperature dependence. The cytokine-induced expression of many (but not all) later genes was insensitive to temperature change (suggesting that they might be functionally temperature-compensated). Moreover, a set of temperature- and TNFα-regulated genes were implicated in NF-κB cross-talk with key cell-fate–controlling pathways. In conclusion, NF-κB dynamics and target gene expression are modulated by temperature and can accurately transmit multidimensional information to control inflammation.

scholarly journals Inhibition of the NF-κB Pathway in Human Intestinal Epithelial Cells by Commensal Streptococcus salivarius

2011 ◽  
Vol 77 (13) ◽  
pp. 4681-4684 ◽  
Author(s):  
Ghalia Kaci ◽  
Omar Lakhdari ◽  
Joël Doré ◽  
S. Dusko Ehrlich ◽  
Pierre Renault ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Streptococcus Salivarius ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Human Intestinal Epithelial Cells ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTStreptococcus salivariusexhibited an anti-inflammatory effect on intestinal epithelial cells (IECs) and monocytes. Strains were screened using a reporter clone, HT-29/kB-luc-E, induced by tumor necrosis factor alpha (TNF-α). Supernatant from each strain downregulated NF-κB activation. The two most efficient strains produced an active metabolite (<3 kDa) which was able to downregulate the secretion of the proinflammatory chemokine interleukin-8 (IL-8).

scholarly journals Blood Cell Fate Decisions: Insights from Single-cell RNA-seq

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. SCI-20-SCI-20
Author(s):  
Merav Socolovsky
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Cell Fate ◽  
Terminal Differentiation ◽  
S Phase ◽  
Erythroid Cell ◽  
Hematopoietic Progenitors ◽  
Erythroid Progenitor ◽  
Cell Fate Decisions ◽  
Computational Predictions

The manner by which multipotent hematopoietic progenitors commit to the erythroid lineage, and the subsequent processes that govern early erythroid progenitor development, are not well understood. Part of the challenge for investigating these was the lack of a rigorous strategy for isolating directly from tissue the early erythroid progenitors, which are functionally defined as the cell 'units' that give rise to erythroid colonies (CFU-e) or bursts (BFU-e) in culture. Indeed, the early erythroid trajectory, that starts with multi-potential progenitors and gives rise to BFU-e, CFU-e and to erythroblasts undergoing terminal differentiation, was not fully elucidated. We addressed these gaps using single cell transcriptomics, combined with functional assays that validated computational predictions 1. These showed that early hematopoietic progenitors form a continuous, hierarchical branching structure, in which the erythroid and basophil/mast cell fates are unexpectedly coupled. We delineated a novel flow-cytometric strategy that prospectively isolates CFU-e and BFU-e progenitors with high purity, and in combination with computational predictions, identified novel growth factor receptors that regulate early erythropoiesis. We further discovered that early erythroid development entails profound remodeling of both G1 and S phases of the cycle, resulting in cell cycle specializations that orchestrate the developmental process, including a gradual shortening of G1 during the CFU-e phase, followed by a sharp increase in the speed of S phase during the S-phase dependent activation of the erythroid terminal differentiation program 1-3(Figure 2). 1. Tusi BK, Wolock SL, Weinreb C, et al. Population snapshots predict early haematopoietic and erythroid hierarchies. Nature. 2018;555(7694):54-60. 2. Hwang Y, Futran M, Hidalgo D, et al. Global increase in replication fork speed during a p57KIP2-regulated erythroid cell fate switch. Science Advances. 2017;3:e1700298. 3. Pop R, Shearstone JR, Shen Q, et al. A key commitment step in erythropoiesis is synchronized with the cell cycle clock through mutual inhibition between PU.1 and S-phase progression. PLoS Biol. 2010;8(9). Disclosures No relevant conflicts of interest to declare.

scholarly journals Role of Eosinophils and Tumor Necrosis Factor Alpha in Interleukin-25-Mediated Protection from Amebic Colitis

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Zannatun Noor ◽  
Koji Watanabe ◽  
Mayuresh M. Abhyankar ◽  
Stacey L. Burgess ◽  
Erica L. Buonomo ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Mouse Model ◽  
Tumor Necrosis ◽  
Intestinal Epithelial ◽  
Necrosis Factor Alpha ◽  
Amebic Colitis ◽  
Tnf Α ◽  
Factor Alpha ◽  
Interleukin 25 ◽  
Necrosis Factor

ABSTRACT The parasite Entamoeba histolytica is a cause of diarrhea in infants in low-income countries. Previously, it was shown that tumor necrosis factor alpha (TNF-α) production was associated with increased risk of E. histolytica diarrhea in children. Interleukin-25 (IL-25) is a cytokine that is produced by intestinal epithelial cells that has a role in maintenance of gut barrier function and inhibition of TNF-α production. IL-25 expression was decreased in humans and in the mouse model of amebic colitis. Repletion of IL-25 blocked E. histolytica infection and barrier disruption in mice, increased gut eosinophils, and suppressed colonic TNF-α. Depletion of eosinophils with anti-Siglec-F antibody prevented IL-25-mediated protection. In contrast, depletion of TNF-α resulted in resistance to amebic infection. We concluded that IL-25 provides protection from amebiasis, which is dependent upon intestinal eosinophils and suppression of TNF-α. IMPORTANCE The intestinal epithelial barrier is important for protection from intestinal amebiasis. We discovered that the intestinal epithelial cytokine IL-25 was suppressed during amebic colitis in humans and that protection could be restored in the mouse model by IL-25 administration. IL-25 acted via eosinophils and suppressed TNF-α. This work illustrates a previously unrecognized pathway of innate mucosal immune response.

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