New knowledge on lymphoid cell maturity could lead to more effective IBD therapies

Date:
April 15, 2022
Source:
Karolinska Institutet
Summary:
A research group has analyzed how certain immune cells known as
innate lymphoid cells (ILCs) develop into mature cells that play a
part in inflammatory bowel disease (IBD). The findings could pave
the way for more effective treatments against IBD, a disease that
causes considerable suffering and that is linked to an increased
risk of colorectal cancer.



FULL STORY ==========================================================================
A research group at Karolinska Institutet in Sweden has analysed how
certain immune cells known as innate lymphoid cells (ILCs) develop into
mature cells that play a part in inflammatory bowel disease (IBD). The
findings could pave the way for more effective treatments against IBD,
a disease that causes considerable suffering and that is linked to an
increased risk of colorectal cancer. The results are published today in
the journal Science Immunology.


========================================================================== Inflammatory bowel disease (IBD) is characterised by a chronic
inflammation of the gut mucosa that is thought to increase the risk of
colon cancer. The disease often debuts before middle age with symptoms
such as abdominal pain and weight loss. The cause is unknown but
genetical, environmental and immunological factors are all believed to
play a role. As a large group of IBD patients do not respond to available treatments, there is a great need for new knowledge about the mechanisms driving the disease.

ILCs are lymphocytes, a family of immune cells, found in the mucosa
where they form part of the immune system and maintain tissue function,
such as the production of mucous. Previous research has shown that ILCs
change function during inflammation, making them a promising target for
IBD treatment.

In the present study, the researchers isolated ILCs from the tonsils and
gut tissue of patients who had undergone resection surgery or endoscopic examination. A total of 48 patients were involved in the study, 31 of
whom had IBD. The ILCs were then examined in detail, both immediately
after isolation and after cell culture.

The results show that a subgroup of ILCs constitute a pre-stage of mature
ILCs and accumulate in the intestinal mucosa of patients with IBD. Factors
in the gut environment can then influence the metabolism of the immature
ILCs, stimulate increased cell division and production of cytokines,
including IL-22, which helps to protect the intestinal tissue.

"The function of ILCs changes during inflammation and therefore
ILCs represent a promising therapeutic target for conditions like
inflammatory bowel disease," says the study's first author Efthymia
Kokkinou, doctoral student at the Department of Medicine, Huddinge
at Karolinska Institutet. "Insight into how these cells develop from
immature cells into mature cells in tissue helps us understand how they influence tissue function or inflammation in mucosa and how they can be manipulated for therapeutic purposes.

The research group now hopes to study if the presence and properties
of immature intestinal ILCs can predict responses to medical drugs, particularly those containing the active substances ustekinumab,
infliximab and tofacitinib, which are currently used to treat Crohn's
disease and ulcerative colitis, two of the most common IBDs.

"These studies are important since the right choice of effective
treatment can reduce both personal suffering and societal costs," says
Jenny Mjo"sberg, associate professor at the same department at Karolinska Institutet and the study's senior author.

The study was mainly financed through an ERC starting grant and by the
Erling- Persson Foundation, the Swedish Research Council, the Swedish
Cancer Society, the Swedish Foundation for Strategic Research, the Knut
and Alice Wallenberg Foundation and Karolinska Institutet.


========================================================================== Story Source: Materials provided by Karolinska_Institutet. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Efthymia Kokkinou, Ram Vinay Pandey, Luca Mazzurana, Irene
Gutierrez-
Perez, Christopher Andrew Tibbitt, Whitney Weigel, Tea
Soini, Anna Carrasco, Anna Rao, Maho Nagasawa, Suzanne
M. Bal, Mattias Jangard, Danielle Friberg, Ulrik Lindforss,
Caroline Nordenvall, Malin Ljunggren, Staffan Haapaniemi,
AAsa V. Keita, Johan So"derholm, Charlotte Hedin, Hergen Spits,
Yenan T. Bryceson, Jenny Mjo"sberg. CD45RA CD62L - ILCs in human
tissues represent a quiescent local reservoir for the generation
of differentiated ILCs. Science Immunology, 2022; 7 (70) DOI:
10.1126/ sciimmunol.abj8301 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220415163754.htm

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