Inflammatory bowel disease linked to an immune cell run amok

Date:
August 24, 2020
Source:
University of California - San Diego
Summary:
Researchers report that the lasting nature of inflammatory bowel
disease may be due to a type of long-lived immune cell that can
provoke persistent, damaging inflammation in the intestinal tract.



FULL STORY ========================================================================== Inflammatory bowel disease (IBD) is a group of intestinal disorders
affecting an estimated six to eight million people worldwide. Although
there are many treatments for IBD, a number of patients fail to respond long-term, leaving those afflicted with a host of chronic issues, from abdominal pain and cramping to frequent, bloody stools.


==========================================================================
In a new study, published August 21, 2020 in Science Immunology, an international team of researchers, led by scientists at University of California San Diego School of Medicine, report that the lasting nature
of IBD may be due to a type of long-lived immune cell that can provoke persistent, damaging inflammation in the intestinal tract.

Led by co-senior authors John T. Chang, MD, professor of medicine,
and Gene W.

Yeo, PhD, professor of cellular and molecular medicine, the research
team performed mRNA and antigen receptor sequencing from immune cells
isolated from samples taken from rectal biopsies or blood of IBD patients
and healthy controls.

"We took advantage of a state-of-the-art approach allowing us to
generate mRNA and antigen receptor sequencing data from the same
single-cells," said Yeo, "and analyzed thousands of individual cells,
which is quite exciting." It has long been believed that immune system dysfunction, in concert with genetic susceptibility and changes in the
gut microbiome, plays a significant role in IBD. However, the types
of immune cells involved and their specific contributions to IBD have
remained unclear. CD8+ T cells are one component of the immune system
that identify and kill cells infected by microbial pathogens.

When an infection has been conquered, the immune system leaves behind
long- lasting cells called memory T cells, which reside in tissues or
circulate through the body remembering past pathogens, ever ready to
sound the alarm should specific invaders reappear.



========================================================================== Chang and Yeo, along with co-first authors Brigid S. Boland, MD, Zhaoren
He, PhD, Matthew S. Tsai, MD PhD, and colleagues, discovered that there
appear to be several subtypes of CD8+ tissue-resident memory T (TRM)
cells, a specific class of memory cell that resides in organs once formed.

One of these TRM cell subtypes was distinguished by high levels of
the transcription factor Eomesodermin and programmed to produce large
amounts of cytokines and other molecules to kill newly detected infected
cells. The downside is that excessive, persistently high levels of some cytokines can cause inflammation and tissue damage.

"We found that this inflammatory TRMcell subtype seemed to be enriched
in the intestinal tissues of patients with ulcerative colitis, a form
of IBD that affects the colon," said Chang. "Long-lived memory cells
are a goal of vaccines, but this finding suggests that these same cells, coveted in the fight against infectious diseases, may actually be harmful
in the context of IBD." The researchers also found evidence that this inflammatory TRM cell subtype might not remain confined to intestinal
tissue, but may also escape into the bloodstream.

"This may explain why IBD can affect not just the intestines, but many
other parts of the body as well," said Boland, a gastroenterologist at
UC San Diego Health and assistant adjunct professor of medicine.

Chang said the findings may help to explain why IBD is chronic and
life-long, and point to the possibility of a remedy in the future:
Targeting this inflammatory TRM cell subtype for elimination, thus ending
the cycle of inflammation and tissue damage.

The researchers noted that much more work is needed to gain a deeper understanding of the role of tissue-resident memory T cells in IBD and
to determine whether they can be targeted therapeutically.


========================================================================== Story Source: Materials provided by
University_of_California_-_San_Diego. Original written by Scott
LaFee. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Brigid S. Boland, Zhaoren He, Matthew S. Tsai, Jocelyn G. Olvera,
Kyla D.

Omilusik, Han G. Duong, Eleanor S. Kim, Abigail E. Limary, Wenhao
Jin, J.

Justin Milner, Bingfei Yu, Shefali A. Patel, Tiani L. Louis, Tiffani
Tysl, Nadia S. Kurd, Alexandra Bortnick, Lauren K. Quezada, Jad N.

Kanbar, Ara Miralles, Danny Huylebroeck, Mark A. Valasek,
Parambir S.

Dulai, Siddharth Singh, Li-Fan Lu, Jack D. Bui, Cornelis Murre,
William J. Sandborn, Ananda W. Goldrath, Gene W. Yeo, John T. Chang.

Heterogeneity and clonal relationships of adaptive immune cells
in ulcerative colitis revealed by single-cell analyses. Science
Immunology, 2020; 5 (50): eabb4432 DOI: 10.1126/sciimmunol.abb4432 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200824160403.htm

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