scholarly journals The Intestinal Stem Cell Compartment is the Initial Target of T Cell Invasion in GI Gvhd

2018 ◽  
Vol 24 (3) ◽  
pp. S67
Author(s):  
Ya-Yuan Fu ◽  
Anastasiya Egorova ◽  
Catherine Sobieski ◽  
Marco Calafiore ◽  
Hans Clevers ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Cell Invasion ◽  
Intestinal Stem Cell ◽  
Cell Compartment ◽  
Stem Cell Compartment ◽  
Initial Target

scholarly journals T Cell Recruitment to the Intestinal Stem Cell Compartment Drives Immune-Mediated Intestinal Damage after Allogeneic Transplantation

Immunity ◽  
2019 ◽  
Vol 51 (1) ◽  
pp. 90-103.e3 ◽  
Author(s):  
Ya-Yuan Fu ◽  
Anastasiya Egorova ◽  
Catherine Sobieski ◽  
Jason Kuttiyara ◽  
Marco Calafiore ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Allogeneic Transplantation ◽  
Intestinal Stem Cell ◽  
Intestinal Damage ◽  
Cell Compartment ◽  
Cell Recruitment ◽  
Stem Cell Compartment ◽  
Immune Mediated

scholarly journals T cell–derived interferon-γ programs stem cell death in immune-mediated intestinal damage

2019 ◽  
Vol 4 (42) ◽  
pp. eaay8556 ◽  
Author(s):  
S. Takashima ◽  
M. L. Martin ◽  
S. A. Jansen ◽  
Y. Fu ◽  
J. Bos ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Paneth Cell ◽  
Interferon Γ ◽  
Cell Compartment ◽  
Stem Cell Compartment ◽  
Immune Mediated ◽  
Donor T Cells ◽  
Epithelial Cultures

Despite the importance of intestinal stem cells (ISCs) for epithelial maintenance, there is limited understanding of how immune-mediated damage affects ISCs and their niche. We found that stem cell compartment injury is a shared feature of both alloreactive and autoreactive intestinal immunopathology, reducing ISCs and impairing their recovery in T cell–mediated injury models. Although imaging revealed few T cells near the stem cell compartment in healthy mice, donor T cells infiltrating the intestinal mucosa after allogeneic bone marrow transplantation (BMT) primarily localized to the crypt region lamina propria. Further modeling with ex vivo epithelial cultures indicated ISC depletion and impaired human as well as murine organoid survival upon coculture with activated T cells, and screening of effector pathways identified interferon-γ (IFNγ) as a principal mediator of ISC compartment damage. IFNγ induced JAK1- and STAT1-dependent toxicity, initiating a proapoptotic gene expression program and stem cell death. BMT with IFNγ–deficient donor T cells, with recipients lacking the IFNγ receptor (IFNγR) specifically in the intestinal epithelium, and with pharmacologic inhibition of JAK signaling all resulted in protection of the stem cell compartment. In addition, epithelial cultures with Paneth cell–deficient organoids, IFNγR-deficient Paneth cells, IFNγR–deficient ISCs, and purified stem cell colonies all indicated direct targeting of the ISCs that was not dependent on injury to the Paneth cell niche. Dysregulated T cell activation and IFNγ production are thus potent mediators of ISC injury, and blockade of JAK/STAT signaling within target tissue stem cells can prevent this T cell–mediated pathology.

scholarly journals The histone variant macroH2A confers functional robustness to the intestinal stem cell compartment

PLoS ONE ◽  
2017 ◽  
Vol 12 (9) ◽  
pp. e0185196 ◽  
Author(s):  
Ryan James Cedeno ◽  
Angela Nakauka-Ddamba ◽  
Maryam Yousefi ◽  
Stephanie Sterling ◽  
Nicolae Adrian Leu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Histone Variant ◽  
Intestinal Stem Cell ◽  
Cell Compartment ◽  
Stem Cell Compartment

Su1203 The Plasticity of the Intestinal Stem Cell Compartment and Its Induction Following Rotavirus Infection

2016 ◽  
Vol 150 (4) ◽  
pp. S494
Author(s):  
Winnie Y. Zou ◽  
Sarah Blutt ◽  
Xi-Lei Zeng ◽  
Umesh C. Karandikar ◽  
Noah F. Shroyer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Intestinal Stem Cell ◽  
Cell Compartment ◽  
Rotavirus Infection ◽  
Stem Cell Compartment

scholarly journals HMGA1 amplifies Wnt signalling and expands the intestinal stem cell compartment and Paneth cell niche

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Lingling Xian ◽  
Dan Georgess ◽  
Tait Huso ◽  
Leslie Cope ◽  
Amy Belton ◽  
...  
Keyword(s):  
Stem Cell ◽  
Paneth Cell ◽  
Wnt Signalling ◽  
Intestinal Stem Cell ◽  
Cell Compartment ◽  
Stem Cell Compartment ◽  
Cell Niche
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