Molecule Strikes Balance in Immune System
and May Be Key to Autoimmune Attack in MS
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Medical Update Memo
June 27, 2008
SUMMARY
Researchers funded by the National MS Society
and others report that a molecule called the
aryl hydrocarbon receptor – which helps
the immune system respond to environmental
toxins – seems to regulate the balance
between inflammatory and anti-inflammatory
cells in MS-like disease in mice. The results
may eventually help tease out the effects of
environmental factors that may trigger the
launch of autoimmune attacks against the nervous
system in MS.
Details
Francisco J. Quintana, PhD, Howard Weiner,
MD (winner of the 2007 Dystel Prize for MS
Research) and colleagues at Havard Medical
School, Boston, report their findings in Nature
(2008 May 1;453[7191]:65-71). This study was
funded by the National MS Society and the National
Institutes of Health among others. Marc Veldhoen,
PhD (MRC National Institute for Medical Research)
and colleagues report similar findings in a
separate article, funded by the Medical Research
Council UK (2008 May 1;453[7191]:106-9).
Multiple sclerosis occurs when the immune
system attacks the brain and spinal cord. The
disease is thought to occur when individuals
whose genes make them susceptible encounter
some unknown triggering factor in their environment.
Numerous cells and proteins participate in
the immune attack. Immune cells called T helper
17 (Th17) cells incite inflammation, whereas
T reg cells are regulatory cells that can suppress
the attack. In people with MS, however, T reg
cells fail to do their jobs, and the attack
goes unchecked. A molecule called aryl hydrocarbon
receptor (AHR), best known for regulating the
immune response to toxins such as dioxin, exists
on the surface of both Th17 cells and T reg
cells; previous research indicates that it
may play a role in their interaction.
Working separately, the two research teams
studied AHR in mice with EAE, an MS-like disease.
Dr. Veldhoen’s group found that inducing
EAE in mice lacking AHR reduced the number
of Th17 cells, without increasing the number
of T reg cells. Dr. Quintana’s group
showed that the results of activating AHR in
EAE depended on the toxin used for activation.
In mice given dioxin, T regs increased their
regulatory activity, decreasing the capabilities
of Th17 cells and suppressing EAE. In mice
given FICZ (another toxin), Th17 cells increased
their activity and EAE worsened.
Taken together, the results may eventually
help tease out the effects of environmental
factors that may trigger the launch of autoimmune
attacks against the nervous system in MS. In
an accompanying editorial, Drs. Emily Stevens
and Christopher Bradfeld (University of Wisconsin,
Madison) explain that the therapeutic ramifications
of these findings, although intriguing, are
still unclear. The key may lie in discovering
why different chemicals affect AHR differently,
which may mimic cues that a developing T cell
receives from the environment. This understanding
is crucial to applying these findings to therapeutic
strategies for autoimmune diseases such as
MS.
With information from the National MS Society (USA)
ASK MS Information System Code: 2.2.m
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Disclaimer
The Multiple Sclerosis Society of Canada is an independent, voluntary health
agency and does not approve, endorse or recommend any specific product or therapy,
but provides information to assist individuals in making their own decisions.
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