Prev: HDAC inhibitors like butyrate reduce autoimmunity via IDO/tryptophan
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From: Kofi on 20 Jul 2008 02:45
This shouldn't come as a shock given that helminths raise regulatory
T-cell numbers and areas with high helminth infection rates have almost
no allergies.

http://www.sciencedaily.com/releases/2008/07/080714155301.htm

Researchers Identify Immune Cells That Block Allergic Reactions

ScienceDaily (July 16, 2008) � When it comes to allergies, both the
problem and the solution are found within us. Our immune systems respond
to foreign substances with an arsenal of cells. Some are programmed to
"remember" invaders they've encountered in the past. Normally, anything
previously identified as harmless is allowed to pass. Sometimes,
however, the immune response goes awry, triggering an allergic reaction.

Now, researchers at NYU Langone Medical Center have zeroed in on a class
of custom-made immune cells that block allergic reactions. These
regulatory T cells are manufactured according to instructions from a
gene called Foxp3 whenever we eat or inhale a potential allergen for the
first time, ensuring that the next time we encounter that substance, we
will not mount an allergic response.

"We don't become allergic to lots of things--we eat all kinds of things,
we breathe all kinds of things, and what prevents us from developing
allergies is that we make regulatory T cells, which specifically
recognize this allergen," says Maria A. Curotto de Lafaille, Ph.D.,
research assistant professor of pathology at NYU Langone Medical Center.
"Every time we don't react to something or don't become allergic, it's
not because nothing is happening," Dr. de Lafaille explains. "It's
because something very important is happening: We're making these cells."

Mucosal tissue, which lines both the respiratory and digestive tracts,
has long been known as an effective barrier against allergens, which are
always protein molecules. The NYU research shows that Foxp3-directed
regulatory T cells (Treg) are produced in the mucosal tissue and remain
there to prevent allergic reactions. New ones are tailor-made every time
an unknown protein is inhaled or ingested. The inability to make Treg
cells results in high susceptibility to becoming allergic.

The NYU researchers induced allergic reactions in mice with a Foxp3
mutation that prevented formation of Treg cells. Exposure to the same
allergen--in this case egg protein--did not elicit an allergic response
in mice that were able to make Treg cells.

The formation of Foxp3-positive Treg cells occurs in response to any
potential allergen, so the findings are applicable to a broad range of
allergic reactions and autoimmune diseases, says Dr. de Lafaille. When
people suffer from allergies, including life-threatening ones such as
asthma, something goes wrong in the process by which Foxp3 signals Treg
cell formation. The problem is not necessarily a mutation in the Foxp3
gene, which is known to cause severe autoimmune disease. Rather,
something occurs, or fails to occur, in the lungs or the gut that
interferes with the production of allergen-specific Treg cells.

The NYU researchers also determined that Treg cells control damage from
long-term inflammation. They found high concentrations of Treg cells in
inflamed lung tissue of mice without the Foxp3 defect. "The question
arose about what these cells are doing in the tissue--are they
beneficial or not?" Dr. de Lafaille says. It turns out that even though
the Treg cells did not prevent inflammation in an ongoing allergic
reaction, they kept it under control, ensuring it did not worsen or
spread to other areas of the body. "We think that over time these
regulatory T cells become more important than the inflammatory cells and
end up completely shutting off the inflammation. But it's not overnight
and it's not black and white," Dr. de Lafaille emphasizes.

This finding provides a key to one of the most serious consequences of
asthma. In addition to breathing problems during an acute attack, people
with asthma have chronic inflammation, which can permanently damage
their lungs. If a means could be found to increase the number of Treg
cells in inflamed tissue, this might be prevented. Allergic asthma, the
most common and best-understood type, affects more than 10 million
people in the US, many of them children. Acute asthma attacks are
responsible for nearly 4000 deaths in the United States each year.

Dr. de Lafaille and her colleagues have been investigating ways to grow
allergen-specific Treg cells in the lab and inject them into people who
cannot make their own. Her group published a paper in Nature Medicine in
February 2008 describing a method of making the cells. "The big
challenge is how to isolate the cells that will recognize the right
allergens that the person is allergic to," she says. Another approach is
to stimulate the body to manufacture the cells itself, an area of
ongoing research.
This work represents an important step in understanding the genetic and
cellular mechanisms underlying the allergic response, which may lead to
more effective therapies. Current treatment is aimed at suppressing
symptoms and reducing inflammation after an allergic reaction has
already occurred. Having identified the cell type that must be present
to prevent allergies, Dr. de Lafaille and her colleagues are now looking
for the glitch that blocks formation of those cells.

The findings are reported in the July 18, 2008, issue of the journal
Immunity. The co-authors of the study include: Dr. de Lafaille, Nino
Kutchukhidze and Shiqian Shen, former postdoctoral students in
pathology, Yi Ding, a graduate student in pathology, and Herman Yee,
M.D., Ph.D., associate professor of pathology, and Juan J. Lafaille,
Ph.D., associate professor of pathology and Medicine at NYU Langone
Medical Center.
The research was supported by grants from the National Institutes of
Health, the National Multiple Sclerosis Society, and the Sandler
Foundation.
------------------------------------------------------------------------
Adapted from materials provided by NYU Langone Medical Center / New York
University School of Medicine, via EurekAlert!, a service of AAAS.

Need to cite this story in your essay, paper, or report? Use one of the
following formats:

APA
MLA
From: MarcusCox2008 on 20 Jul 2008 02:50
And this has to do with hair loss exactly how?


Yes Kofi,

we know you can 'cut & paste', which alone makes you smarter than Dr.
Ernie Primeau.

But why are you x-posting this?

Marcus

On Jul 19, 11:45 pm, Kofi <k...(a)anon.un> wrote:
> This shouldn't come as a shock given that helminths raise regulatory
> T-cell numbers and areas with high helminth infection rates have almost
> no allergies.
>
> http://www.sciencedaily.com/releases/2008/07/080714155301.htm
>
> Researchers Identify Immune Cells That Block Allergic Reactions
>
> ScienceDaily (July 16, 2008) ‹ When it comes to allergies, both the
> problem and the solution are found within us. Our immune systems respond
> to foreign substances with an arsenal of cells. Some are programmed to
> "remember" invaders they've encountered in the past. Normally, anything
> previously identified as harmless is allowed to pass. Sometimes,
> however, the immune response goes awry, triggering an allergic reaction.
>
> Now, researchers at NYU Langone Medical Center have zeroed in on a class
> of custom-made immune cells that block allergic reactions. These
> regulatory T cells are manufactured according to instructions from a
> gene called Foxp3 whenever we eat or inhale a potential allergen for the
> first time, ensuring that the next time we encounter that substance, we
> will not mount an allergic response.
>
> "We don't become allergic to lots of things--we eat all kinds of things,
> we breathe all kinds of things, and what prevents us from developing
> allergies is that we make regulatory T cells, which specifically
> recognize this allergen," says Maria A. Curotto de Lafaille, Ph.D.,
> research assistant professor of pathology at NYU Langone Medical Center.
> "Every time we don't react to something or don't become allergic, it's
> not because nothing is happening," Dr. de Lafaille explains. "It's
> because something very important is happening: We're making these cells."
>
> Mucosal tissue, which lines both the respiratory and digestive tracts,
> has long been known as an effective barrier against allergens, which are
> always protein molecules. The NYU research shows that Foxp3-directed
> regulatory T cells (Treg) are produced in the mucosal tissue and remain
> there to prevent allergic reactions. New ones are tailor-made every time
> an unknown protein is inhaled or ingested. The inability to make Treg
> cells results in high susceptibility to becoming allergic.
>
> The NYU researchers induced allergic reactions in mice with a Foxp3
> mutation that prevented formation of Treg cells. Exposure to the same
> allergen--in this case egg protein--did not elicit an allergic response
> in mice that were able to make Treg cells.
>
> The formation of Foxp3-positive Treg cells occurs in response to any
> potential allergen, so the findings are applicable to a broad range of
> allergic reactions and autoimmune diseases, says Dr. de Lafaille. When
> people suffer from allergies, including life-threatening ones such as
> asthma, something goes wrong in the process by which Foxp3 signals Treg
> cell formation. The problem is not necessarily a mutation in the Foxp3
> gene, which is known to cause severe autoimmune disease. Rather,
> something occurs, or fails to occur, in the lungs or the gut that
> interferes with the production of allergen-specific Treg cells.
>
> The NYU researchers also determined that Treg cells control damage from
> long-term inflammation. They found high concentrations of Treg cells in
> inflamed lung tissue of mice without the Foxp3 defect. "The question
> arose about what these cells are doing in the tissue--are they
> beneficial or not?" Dr. de Lafaille says. It turns out that even though
> the Treg cells did not prevent inflammation in an ongoing allergic
> reaction, they kept it under control, ensuring it did not worsen or
> spread to other areas of the body. "We think that over time these
> regulatory T cells become more important than the inflammatory cells and
> end up completely shutting off the inflammation. But it's not overnight
> and it's not black and white," Dr. de Lafaille emphasizes.
>
> This finding provides a key to one of the most serious consequences of
> asthma. In addition to breathing problems during an acute attack, people
> with asthma have chronic inflammation, which can permanently damage
> their lungs. If a means could be found to increase the number of Treg
> cells in inflamed tissue, this might be prevented. Allergic asthma, the
> most common and best-understood type, affects more than 10 million
> people in the US, many of them children. Acute asthma attacks are
> responsible for nearly 4000 deaths in the United States each year.
>
> Dr. de Lafaille and her colleagues have been investigating ways to grow
> allergen-specific Treg cells in the lab and inject them into people who
> cannot make their own. Her group published a paper in Nature Medicine in
> February 2008 describing a method of making the cells. "The big
> challenge is how to isolate the cells that will recognize the right
> allergens that the person is allergic to," she says. Another approach is
> to stimulate the body to manufacture the cells itself, an area of
> ongoing research.
> This work represents an important step in understanding the genetic and
> cellular mechanisms underlying the allergic response, which may lead to
> more effective therapies. Current treatment is aimed at suppressing
> symptoms and reducing inflammation after an allergic reaction has
> already occurred. Having identified the cell type that must be present
> to prevent allergies, Dr. de Lafaille and her colleagues are now looking
> for the glitch that blocks formation of those cells.
>
> The findings are reported in the July 18, 2008, issue of the journal
> Immunity. The co-authors of the study include: Dr. de Lafaille, Nino
> Kutchukhidze and Shiqian Shen, former postdoctoral students in
> pathology, Yi Ding, a graduate student in pathology, and Herman Yee,
> M.D., Ph.D., associate professor of pathology, and Juan J. Lafaille,
> Ph.D., associate professor of pathology and Medicine at NYU Langone
> Medical Center.
> The research was supported by grants from the National Institutes of
> Health, the National Multiple Sclerosis Society, and the Sandler
> Foundation.
> ------------------------------------------------------------------------
> Adapted from materials provided by NYU Langone Medical Center / New York
> University School of Medicine, via EurekAlert!, a service of AAAS.
>
> Need to cite this story in your essay, paper, or report? Use one of the
> following formats:
>
>  APA
>  MLA

From: Kofi on 20 Jul 2008 23:36
> And this has to do with hair loss exactly how?
>
>

Helminths raise Treg levels and impair mast cell degranulation,
specifically via IgG4
<http://www.discover.com/issues/sep-93/features/ofparasitesandpo264/>.

Dosing hair follicles with substance P causes mast cell degranulation in
addition to catagen [PMID 18055548]. There is evidence from human scalp
biopsies that this same mast cell degranulation is behind the fibrosis
seen in baldness [PMID 1390168].

This link would be consistent with the observation that as poor Koreans
and Japanese moved from rural to urban areas in the 20th century they
suddenly experienced Western rates of hair loss. The rural water supply
was likely infested with various helminths.

> Yes Kofi,
>
> we know you can 'cut & paste', which alone makes you smarter than Dr.
> Ernie Primeau.

Let's clear something up. I don't care how smart anybody thinks I am.
You or George Bush having a certain opinion about reality doesn't
actually cause reality to conform to your opinion of it.
From: Taka on 21 Jul 2008 09:37
On Jul 20, 3:45 pm, Kofi <k...(a)anon.un> wrote:
> This shouldn't come as a shock given that helminths raise regulatory
> T-cell numbers and areas with high helminth infection rates have almost
> no allergies.
>
> http://www.sciencedaily.com/releases/2008/07/080714155301.htm
>
> Researchers Identify Immune Cells That Block Allergic Reactions
>
> ScienceDaily (July 16, 2008) ‹ When it comes to allergies, both the
> problem and the solution are found within us. Our immune systems respond
> to foreign substances with an arsenal of cells. Some are programmed to
> "remember" invaders they've encountered in the past. Normally, anything
> previously identified as harmless is allowed to pass. Sometimes,
> however, the immune response goes awry, triggering an allergic reaction.
>
> Now, researchers at NYU Langone Medical Center have zeroed in on a class
> of custom-made immune cells that block allergic reactions. These
> regulatory T cells are manufactured according to instructions from a
> gene called Foxp3 whenever we eat or inhale a potential allergen for the
> first time, ensuring that the next time we encounter that substance, we
> will not mount an allergic response.
>
> "We don't become allergic to lots of things--we eat all kinds of things,
> we breathe all kinds of things, and what prevents us from developing
> allergies is that we make regulatory T cells, which specifically
> recognize this allergen," says Maria A. Curotto de Lafaille, Ph.D.,
> research assistant professor of pathology at NYU Langone Medical Center.
> "Every time we don't react to something or don't become allergic, it's
> not because nothing is happening," Dr. de Lafaille explains. "It's
> because something very important is happening: We're making these cells."
>
> Mucosal tissue, which lines both the respiratory and digestive tracts,
> has long been known as an effective barrier against allergens, which are
> always protein molecules. The NYU research shows that Foxp3-directed
> regulatory T cells (Treg) are produced in the mucosal tissue and remain
> there to prevent allergic reactions. New ones are tailor-made every time
> an unknown protein is inhaled or ingested. The inability to make Treg
> cells results in high susceptibility to becoming allergic.
>
> The NYU researchers induced allergic reactions in mice with a Foxp3
> mutation that prevented formation of Treg cells. Exposure to the same
> allergen--in this case egg protein--did not elicit an allergic response
> in mice that were able to make Treg cells.
>
> The formation of Foxp3-positive Treg cells occurs in response to any
> potential allergen, so the findings are applicable to a broad range of
> allergic reactions and autoimmune diseases, says Dr. de Lafaille. When
> people suffer from allergies, including life-threatening ones such as
> asthma, something goes wrong in the process by which Foxp3 signals Treg
> cell formation. The problem is not necessarily a mutation in the Foxp3
> gene, which is known to cause severe autoimmune disease. Rather,
> something occurs, or fails to occur, in the lungs or the gut that
> interferes with the production of allergen-specific Treg cells.
>
> The NYU researchers also determined that Treg cells control damage from
> long-term inflammation. They found high concentrations of Treg cells in
> inflamed lung tissue of mice without the Foxp3 defect. "The question
> arose about what these cells are doing in the tissue--are they
> beneficial or not?" Dr. de Lafaille says. It turns out that even though
> the Treg cells did not prevent inflammation in an ongoing allergic
> reaction, they kept it under control, ensuring it did not worsen or
> spread to other areas of the body. "We think that over time these
> regulatory T cells become more important than the inflammatory cells and
> end up completely shutting off the inflammation. But it's not overnight
> and it's not black and white," Dr. de Lafaille emphasizes.
>
> This finding provides a key to one of the most serious consequences of
> asthma. In addition to breathing problems during an acute attack, people
> with asthma have chronic inflammation, which can permanently damage
> their lungs. If a means could be found to increase the number of Treg
> cells in inflamed tissue, this might be prevented. Allergic asthma, the
> most common and best-understood type, affects more than 10 million
> people in the US, many of them children. Acute asthma attacks are
> responsible for nearly 4000 deaths in the United States each year.
>
> Dr. de Lafaille and her colleagues have been investigating ways to grow
> allergen-specific Treg cells in the lab and inject them into people who
> cannot make their own. Her group published a paper in Nature Medicine in
> February 2008 describing a method of making the cells. "The big
> challenge is how to isolate the cells that will recognize the right
> allergens that the person is allergic to," she says. Another approach is
> to stimulate the body to manufacture the cells itself, an area of
> ongoing research.
> This work represents an important step in understanding the genetic and
> cellular mechanisms underlying the allergic response, which may lead to
> more effective therapies. Current treatment is aimed at suppressing
> symptoms and reducing inflammation after an allergic reaction has
> already occurred. Having identified the cell type that must be present
> to prevent allergies, Dr. de Lafaille and her colleagues are now looking
> for the glitch that blocks formation of those cells.
>
> The findings are reported in the July 18, 2008, issue of the journal
> Immunity. The co-authors of the study include: Dr. de Lafaille, Nino
> Kutchukhidze and Shiqian Shen, former postdoctoral students in
> pathology, Yi Ding, a graduate student in pathology, and Herman Yee,
> M.D., Ph.D., associate professor of pathology, and Juan J. Lafaille,
> Ph.D., associate professor of pathology and Medicine at NYU Langone
> Medical Center.
> The research was supported by grants from the National Institutes of
> Health, the National Multiple Sclerosis Society, and the Sandler
> Foundation.
> ------------------------------------------------------------------------
> Adapted from materials provided by NYU Langone Medical Center / New York
> University School of Medicine, via EurekAlert!, a service of AAAS.
>
> Need to cite this story in your essay, paper, or report? Use one of the
> following formats:
>
> APA
> MLA

Good post, thanks Kofi. Finally some research which taps directly
into the molecular mechanism of allergies and not just another
antihistamine drug. PGE2 stimulates the tolerance via TREGs and
helminths do induce PGE2 (e.g. PMID: 17544219, 18305957,16009364). Is
there something suppressing prostaglandins while increasing
leukotrienes like NSAIDs common to people with allergies? E.g. I was
taking frequently paracetamol (PMID: 17884974) for colds when my
pollen allergies started ...

Taka
From: Kofi on 21 Jul 2008 14:51
In article
<130e46ed-f1de-488d-a1ab-db9a629a4f03(a)79g2000hsk.googlegroups.com>,
Taka <taka0038(a)gmail.com> wrote:

> Good post, thanks Kofi. Finally some research which taps directly
> into the molecular mechanism of allergies and not just another
> antihistamine drug. PGE2 stimulates the tolerance via TREGs and
> helminths do induce PGE2 (e.g. PMID: 17544219, 18305957,16009364). Is
> there something suppressing prostaglandins while increasing
> leukotrienes like NSAIDs common to people with allergies? E.g. I was
> taking frequently paracetamol (PMID: 17884974) for colds when my
> pollen allergies started ...
>

It signals through EP4. Thanks. I missed the prostaglandin/helminth
link.

COX-2 inhibitors do directly depress Treg function, thus - according to
this lastest paper - elevating allergies. COX-2 inhibition will also
worsen pretty much any form of autoimmunity you've got (and block stem
cells from their repair work, hence shrinking joints and impairing the
healing process all over the body). The direct mechanism on Tregs has
been understood since 2005 but people were noticing how the
prostaglandin network regulated antigen tolerance a long time before
that. The FDA has failed to warn anybody about this.

FYI, helminths also deplete iron (see my earlier posts on the
gut-protective HIF-1a pathway and iron chelators/prolyl hydroxylase
inhibitors) and, the last time I went hunting for it, there was even
tantalizing evidence the critters produce butyrate in the gut.

Do you know anything about beta-glucuronidase and any of these topics?
It's a very effective therapy for inducing tolerance to allergens. You
need about four shots a year to maintain your protection. I know it's
related to heparanse and that sticks it somewhere in the HIF network but
that's about all I got.

_______________________________________________

in lung cancer, COX-2 and PGE2 underlie an immunosuppressive network
that is important in the formation of non-small cell lung cancer; CD4+
CD25+ regulatory T-cells (Tregs) block antitumor immune responses when
tumors secrete PGE2 and activate Foxp3 in the Tregs which increases Treg
activity; this effect was significantly reduced without an EP4
(E-prostanoid) receptor and totally absent without an EP2 receptor;
COX-2 inhibitors (Vioxx, Celebrex) reduced Treg activity, blocked FoxP3
and decreased tumor growth (this provides a pathway whereby COX-2
inhibitors can exaggerate allergies) [PMID 15958566]

broad-spectrum COX inhibitors can be arthritigenic interfering with the
acquisition of tolerance to some arthritigens [PMID 16259716]
 | 
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