Research: Crohn's blamed on lazy immune cells
zumone2002
Crohn's blamed on lazy immune cells
* 19 November 2009 by Linda Geddes
A MYSTERIOUS bowel disease thought to be caused by an over-exuberant
immune system may paradoxically be triggered by immune cells that
don't do enough in the early stages of bacterial infection.
Since some treatments for Crohn's disease aim to suppress the immune
system, it's possible these drugs could be making things worse. The
discovery by Anthony Segal of University College London and his
colleagues is causing a stir among immunologists. Caetano Reis e Sousa
at Cancer Research UK calls it "provocative", while Jean-Laurent
Casanova at The Rockefeller University in New York says it is "a major
breakthrough".
A similar mechanism may be at the root of a host of other "autoimmune"
disorders, in which immune cells turn on the body's own tissue.
Underactive immune cells could also explain why some of us are more
prone to infectious diseases.
About 1 in 1000 people in the US and Europe have Crohn's. Symptoms
include swollen, painful intestines and diarrhoea. Inflamed sections
of gut often have to be surgically removed.
Segal and his colleagues got their first clue when they noticed a
weaker immune response in people with Crohn's than in healthy people
after both groups were injected with heat-killed Escherichia coli. The
team reasoned that this lukewarm response might allow an infection to
build up and eventually trigger a debilitating secondary immune
response, resulting in Crohn's.
If this is the case, though, why does Crohn's only manifest itself in
the intestine? After further experiments it became clear that the
immune weakness only revealed itself when large numbers of killed E.
coli were injected. As the bowel is one of the few places in the body
where bacteria exist in huge numbers, Segal concluded that this is
where the weakened immune response has its biggest impact. "It's only
in the bowel that you routinely get massive loads of bacteria - and if
these breach the intestinal wall it will cause an infection."
It still wasn't clear, however, what caused the weakened immunity in
the first place. So Segal's team focused on cells called macrophages,
the immune system's whistle-blowers. In people with Crohn's disease,
they found that macrophages secrete lower levels of cytokines, the
chemicals that rally other immune cells to infection sites (Journal of
Experimental Medicine, DOI: 10.1084/jem.20091683).
The team concluded that ineffectual rallying of immune cells in people
with defective macrophages is what allows intestinal bacteria to run
amok in the early stages of an infection, setting in motion the series
of events that leads to Crohn's disease.
In Crohn's the immune system's whistle-blowers are bad at rallying
other cells to fight infection
Now Segal would like to look at the role of defective macrophages in
other autoimmune diseases, such as rheumatoid arthritis and psoriasis.
Casanova suspects that they may also leave people more susceptible to
illnesses such as tuberculosis. "Macrophages are central to many
physiological processes," he adds.
--
Luke
Professor Anthony W Segal's web page http://www.ucl.ac.uk/slms/people/show.php?personid=12245