Th17 & Gut Psor Musings -- ID3 & GammaDelta T cells --PLUS more...
randall
How long have I been saying what this next article says?
But I didn't know how or WHY Th-17 does it's thing down under?
Till only a few years ago, who did?
OK, right..researcher's only suspected that ALL autoimmune
inflammation due to Th17
was subclinacal and of a gut tract orgin?
But NOW they KNOW?
It's coming..
http://www.medpagetoday.com/Gastroenterology/InflammatoryBowelDisease/16472
Gut Bacteria Linked to Immune Response
By Michael Smith, North American Correspondent, MedPage Today
Published: October 16, 2009
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of
Medicine, Harvard Medical School, Boston.
Specific bacteria in the gut may stimulate the immune system --
helping to fight infection in some cases, but perhaps also playing a
role in autoimmune disease, researchers said.
At least that's proven to be the case in mice, where so-called
segmented filamentous bacteria stimulated the production of Th17
helper cells, according to two research groups, working independently.
The finding is the "first example of commensal bacteria that can
induce accumulation in the gut of a highly specific branch of the
immune system," according to Dan Littman, MD, PhD, of the Skirball
Institute of Biomolecular Medicine in New York City.
With colleagues, Littman reported online in Cell that colonization of
the small intestine of mice by the microbes is sufficient to induce
CD4-positive T cells that produce interleukin 17 and 22.
Those Th17 cells play a role in protecting against bacterial and
fungal infections but also are key mediators of autoimmune disease,
the researchers noted.
Their findings are paralleled by a report in the Oct. 16 issue of
Immunity from Valérie Gaboriau-Routhiau, PhD, of the French National
Institute for Health and Medical Research in Paris, and colleagues.
A surprising aspect of the research, Gaboriau-Routhiau said in a
statement, is that the segmented filamentous bacteria appear to be the
only microbes that have the effect.
"For us, it was first a surprise to observe so little redundancy in
the role of commensal bacteria on stimulating immune responses,"
Gaboriau-Routhiau said.
For Littman and colleagues, the findings were serendipitous. They had
been studying the immune response of mice and noted that commercially
available experimental animals had marked differences in the
proportion of Th17 cells in the gut.
Experiments showed that they also had differences in the composition
of the gut bacteria, the researchers reported, and that cross-
infecting animals could induce Th17 cells where there had been few or
none.
Using microarray technology, they compared animals that had Th17 cells
in the gut with those that did not, looking for differences in
bacterial species.
They found that 479 microbial groups (out of 766) were significantly
different (at P<0.05) but that most were subtle -- less than a five-
fold difference.
On the other hand, there was more than a 25-fold difference in two
species -- identified as Lactobacillus murinus ASF361 and a segmented
filamentous species of the candidate genus Arthromitus.
Both were significantly higher (at P<0.001) in the mice with Th17
cells than in those without, the researchers found.
But when they colonized germ-free mice with L. murinus, the bacteria
did not induce any Th17 cells. Colonization with the segmented
filamentous bacteria, on the other hand, led to a vigorous Th17
response within 10 days.
In another experiment, colonization with the bacteria reduced the
effects of an infection with Citrobacter rodentium, an intestinal
pathogen in mice that is considered a good model for disease-causing
Escherichia coli.
If the effect is present in humans, it suggests a clinical use for the
findings, Littman said. "So you can immediately see some practical
application of this, if one can mimic the presence of these commensal
bacteria to strengthen resistance to pathogenic microbes," he said.
On the other hand, the level of the microbes could also play a role in
the development of autoimmune disease, he said. "You have to have the
right balance," Littman said.
<sniP>
----
Their abstract isn't available, but this is:::
http://www.cell.com/abstract/S0092-8674(09)01248-3
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Summary
The gastrointestinal tract of mammals is inhabited by hundreds of
distinct species of commensal microorganisms that exist in a
mutualistic relationship with the host. How commensal microbiota
influence the host immune system is poorly understood. We show here
that colonization of the small intestine of mice with a single
commensal microbe, segmented filamentous bacterium (SFB), is
sufficient to induce the appearance of CD4+ T helper cells that
produce IL-17 and IL-22 (Th17 cells) in the lamina propria. SFB adhere
tightly to the surface of epithelial cells in the terminal ileum of
mice with Th17 cells but are absent from mice that have few Th17
cells. Colonization with SFB was correlated with increased expression
of genes associated with inflammation and antimicrobial defenses and
resulted in enhanced resistance to the intestinal pathogen Citrobacter
rodentium. Thus, manipulation of this commensal-regulated pathway may
provide new opportunities for enhancing mucosal immunity and treating
autoimmune disease.
<sniP>
=================
http://www.sciencedaily.com/releases/2009/10/091015123550.htm
Process That Determines Fate Of White Blood Cells Uncovered
ScienceDaily (Oct. 15, 2009) — Like an unusually forceful career
counselor, the Id3 protein decides the fate of a given white blood
cell precursor, according to researchers at Fox Chase Cancer Center.
Their findings, published today in the journal Immunity, describe how
Id3 directs blood cell progenitors to become gamma-delta T cells.
Gamma-delta T cells are unique in that they possess attributes of both
the adaptive arm of the immune system, which is invigorated by
vaccination, and the innate arm, which represents the body's first
line of defense against infections.
"Unlike the other major type of T cells (alpha-beta), gamma-delta T
cells seem to focus most of their efforts on protecting the body
surfaces in contact with the outside world, like skin, gut, and lung
and in fact are required to repel invaders at those sites," says co-
author David Wiest, Ph.D., Fox Chase professor and co-leader of the
center's Immune Cell Development and Host Defense Program. "Their
origins have been something of a mystery and, as it turns out, their
creation requires distinct molecular machinery than the other major
type of T cells."
In recent years, studying the origins of blood cells has provided
researchers with useful insights on how all the cells in the body form
from a small group of embryonic stem cells. All blood cells originate
from a type of stem cell – called hematopoietic ("blood-forming") stem
cells – located in bone marrow. A small portion of these cells move on
to the thymus – a small organ near the lungs – where their ultimate
fate as one of many types of white blood cells is decided through a
series of molecular pathways.
Among these cells are T cells, of which there are two recognized
types, based on the structure of their most defining feature, the T
Cell Receptor (TCR), which enables the cell to detect bits of foreign
molecules called antigens. The majority of T cells are alpha-beta T
cells, meaning their TCR are comprised of alpha and beta subunits.
Only five percent of T cells are gamma-delta T cells, yet researchers
believe that they have a remarkable effect on human health.
Using a mouse model of human blood cell development, Wiest and his
colleagues demonstrated that gamma-delta T cells require the Id3 gene
for formation. Moreover, they showed that elevating the levels of Id3
alone was sufficient to push progenitor cells in the thymus into
becoming delta-gamma T cells. This is not true of the development of
other major T lineage, alpha-beta, for which the function of Id3 is
dispensable.
One of the weapons utilized by gamma-delta cells is a substance called
interferon-gamma, which has known anti-viral and anti-tumor
properties. Interferon-gamma is also known to contribute inflammation
at the site of infection, such as a wound, but also may be a source of
autoimmune disease.
"By better understanding the process that drives gamma-delta T cell
production, we may one day become capable of producing them outside of
the body for use as a therapy in people when warranted," Wiest says.
"While we are only beginning to understand the functions of gamma-
delta T cells, one setting where they might be useful therapeutically,
is cancer," Wiest says, "since gamma-delta T cells seem to be well
equipped to combat cutaneous malignancies."
Funding for this research comes from grants from the National
Institutes for Health, an appropriation from the Commonwealth of
Pennsylvania, and the Fox Chase Keystone Program in Blood Cell
Development and Cancer.
------
http://en.wikipedia.org/wiki/Skin
http://en.wikipedia.org/wiki/Integumentary_system
http://en.wikipedia.org/wiki/Skin_disease
http://en.wikipedia.org/wiki/Dermatology
http://en.wikipedia.org/wiki/List_of_skin_diseases
====================
You want more mitochondrial in your cells?
Hell YEAH....
Who doesn't?
Eat less protein and grow them GERM critter's?
http://www.lef.org/newsletter/2009/1013_Low-Protein-Diet-Improves-Mitochondrial-Function.htm
Low protein diet improves mitochondrial function
A dietary regimen that is the opposite of the high protein Atkins diet
was associated with a longer lifespan and improved mitochondrial
function in research conducted with flies at the Buck Institute for
Age Research in Novato, California. Reduced functioning of the
mitochondria, which are the power plants of the cells, occurs with
aging and is associated with such diseases such as type 2 diabetes and
Parkinson's disease.
In the October 2, 2009 issue of the journal Cell, Pankaj Kapahi, PhD
and colleagues identify the mechanism of the extension of life span
observed in flies whose diets were modified by lowering the level of
yeast relative to sucrose (the source of carbohydrates in the flies'
diets). By examining the expression of genes in restricted flies, Dr
Kapahi and his associates found that, although protein synthesis was
reduced on a global level, the activity of specific genes involved in
the production of energy within the mitochondria increased. According
to Dr Kapahi, this activity, which occurs at the level of conversion
of RNA to protein, is involved in dietary restriction's protective
effects. Flies receiving low protein diets showed increased activity
of a protein known as d4EBP, which is part of a signaling pathway
called TOR (target of rapamycin) that influences cell growth in
response to the availability of nutrients. (Rapamycin, a drug that has
many medical uses, was recently shown to increase the lifespan of aged
mice.) While flies on a low protein diet experienced a significant
extension of lifespan compared to flies whose diets were
nonrestricted, knocking out the gene for d4EBP diminished the effect,
and restoring d4EBP expression enhanced it.
The findings question the wisdom of popular high protein weight loss
diets. "In flies, we see that the long-lived diet is a low protein
diet and what we have found here is a mechanism for how that may be
working." Dr Kapahi stated.
The study is the first genome-wide investigation of how proteins are
translated in dietary restricted organisms. "Our study shows that
dietary restriction can enhance mitochondrial function hence
offsetting the age-related decline in its performance," Dr Kapahi
concluded. "There have been correlative studies that show mitochondria
change with dietary restriction; this research provides a causal
relationship between diet and mitochondrial function."
<sniP>
http://en.wikipedia.org/wiki/Mitochondrial
http://en.wikipedia.org/wiki/Mitochondrial_DNA
http://en.wikipedia.org/wiki/Mitochondrial_DNA#Female_inheritance
The GERM outa Africa from EVE:
http://en.wikipedia.org/wiki/Mitochondrial_Eve
=============
If you are going to eat protein which WHEY to GO is for YOU.
http://www.wellnessresources.com/health/articles/which_whey_to_go/
Which Whey to Go
Friday, October 09, 2009 - Byron J. Richards, CCN
Newsletter Details
In the world of dietary supplements and functional foods there are
many choices in terms of product quality, and whey protein is no
exception. This is especially true when a used-car sales pitch is
used in an effort to make products look and sound far better than what
is actually under the hood. While consumers should expect this from
network marketing companies they are often taken aback when health
professionals go out on a limb and push the envelope of truth.
There are two main types of whey protein used in protein drink
formulations: whey protein concentrates and whey protein isolates.
<sniP>
Helps boost glutathione.
Is that enough for you?
Should be, as well as for ME.
================
Want to grow your hair and nails super fast?
LOL-- no.
But go on.
Take biotin and chromium picolinate
www.vrp.com
Support Blood Sugar, Hair and Nail Growth…with a Single Vitamin
Health News
By VRP Staff
Brace yourself… because you’re about to hear the opening shots of a
two-month-long assault on your blood sugar. With Halloween just a
couple of weeks away and another holiday season right around the
corner, it’s that time of year once again— promising weeks of food,
drink, and a hefty helping of stress. It’s the beginning of a bumpy
ride for everyone’s health.
Unfortunately, sitting out of the next two months isn’t an option. But
the good news is that research shows you can safely soldier through
this year’s sugar binge—with an extra daily dose of one critical B
vitamin. What’s more, this vitamin is tied to healthy hair and nails
as well.
In a study of 43 obese or overweight subjects, researchers at Yale
University set out to examine the effects of biotin supplementation on
blood sugar control in treatment-resistant cases of type 2 diabetes.
Over the course of four weeks, subjects were randomized to receive
either a combination of 600 mcg of chromium picolinate and 2 mg of
biotin per day, or a placebo treatment. Researchers measured both
groups’ glycemic control and blood lipid levels at the beginning and
end of the trial period.
After four weeks, glucose tolerance tests showed a 15 percent
improvement in blood sugar control among subjects taking the biotin
and chromium picolinate combo—a significantly better response than the
placebo group.1 What’s more, triglyceride levels also decreased in the
experimental group—while in stark contrast, subjects taking a placebo
showed significant increases in serum levels of these dangerous
lipids.
The best news? No major adverse events were reported among patients
taking biotin—which means that this natural therapy is as safe as it
is effective. And to top it off, additional research shows that it
might come with at least one pleasant perk.
Ask anyone who’s supplemented with biotin for 60 days or longer, and
you may be surprised to hear reports of increased hair and nail
growth, too. Research reveals that more than half of all subjects with
brittle nails will see as much as a 25 percent improvement in nail
quality after treatment with biotin over a six month period—marked by
significantly less splitting and greater regularity in nail bed
surface cell arrangement.2-3
The bottom line: Whether you’re struggling with blood sugar control,
slow hair growth or broken nails, boosting your intake of biotin could
turn out to be your best solution yet. You can find this potent B
vitamin as a daily supplement, readily available through Vitamin
Research Products.
<sniP>
====================
http://articles.mercola.com/sites/articles/archive/2009/10/13/Dr-Oz-Helps-Shill-the-Flu-Vaccine.aspx
Dr. Mehmet OZ and his family will NOT be getting the swine flu shot?
=============
The novel pathogenetic cascade of Psoriasis?
www.ncbi.nlm.nih.gov/pubmed/19830738
The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: A
novel immunological cascade with potential relevance in psoriasis.
Wolk K, Witte E, Warszawska K, Schulze-Tanzil G, Witte K, Philipp S,
Kunz S, Döcke WD, Asadullah K, Volk HD, Sterry W, Sabat R.
Interdisciplinary Department of Molecular Immunopathology, Dermatology/
Medical Immunology, University Hospital Charité, 10117 Berlin,
Germany.
Psoriasis is a common chronic skin disease. Recent studies
demonstrated that IL-20 and IL-22, cytokines produced by keratinocytes
and T-cells, respectively, both inhibit keratinocyte terminal
differentiation and induce psoriasis-like epidermis alterations. Here,
we investigated the relationship between these mediators. Whereas
IL-20 was not able to regulate IL-22 production, IL-22 induced IL-20
mRNA and protein in human keratinocytes. However, IL-22 had only a
minimal effect, if any, on IL-19 and IL-26. Cutaneous IL-20 was also
elevated in mice following IL-22 application. Accordingly, some of the
IL-22 effects on differentiation regulating genes were partially
mediated by an endogenous, secreted protein and attenuated by anti-
IL-20 antibodies. Like IL-22, IL-17A and TNF-alpha induced IL-20 in
keratinocytes, whereas IFN-gamma and IL-20 itself did not.
Furthermore, IL-17A and TNF-alpha individually strengthened the IL-22-
induced IL-20 production. In lesional skin of psoriasis patients,
highly elevated IL-20 levels strongly correlated with IL-22, and to a
lesser extent, with IL-17A and TNF-alpha. As previously shown for
IL-22, IL-20 blood levels correlated with the disease severity,
although with a lower significance. This study demonstrates that a T-
cell mediator induces a tissue cell mediator with similar effects to
its own and therefore suggests the existence of a novel type of
pathogenetic cascade.
PMID: 19830738
Calling ALL psor head scuba divers with the BENDs.
Time to HEAL those psors with the yperbaric chamber?
www.ncbi.nlm.nih.gov/pubmed/19830133
Therapeutic effect of hyperbaric oxygen in psoriasis vulgaris: two
case reports and a review of the literature.
Butler G, Michaels JC, Al-Waili N, Finkelstein M, Allen M, Petrillo R,
Carrey Z, Kolanuvada B, Lee BY, Riera AG, Michaels CC, Urteaga G.
INTRODUCTION: Psoriasis is an inflammatory and immunological cutaneous
disease. The high morbidity in patients with psoriasis results from
severe clinical manifestations and/or adverse effects of treatment.
The Undersea and Hyperbaric Medical Society and Federal Medicare and
Medicaid Services have approved the use of hyperbaric oxygen (HBO(2))
for more than 15 indications, including wound healing, infections and
late effects of radiation, which are largely unresponsive to
conventional treatments. Accumulated data show that HBO(2) has anti-
inflammatory effects and other positive influences on the immune
system, making it a rational treatment in the management of psoriasis
plaques and arthritis. CASE PRESENTATION: We present the cases of two
patients with long histories of psoriasis vulgarus who exhibited
marked improvement with use of HBO(2.) The first patient was 40 years
old and had pustular psoriasis and psoriatic arthritis. He was treated
with six sessions of HBO(2) (at 2.8 atmospheres of pressure for 60
minutes), which successfully controlled his symptoms. At the 18-month
post-treatment follow up, the patient exhibited complete remission of
psoriasis and marked improvement in psoriatic arthritis without
medication. The second patient was 55 years old with extensive
psoriatic lesions, and exhibited marked improvement within 15 sessions
of HBO(2). No adverse effects of HBO(2) were identified. CONCLUSIONS:
HBO(2) may possess potential therapeutic efficacy in the management of
psoriasis. We outline the pathogenesis of psoriasis and the selective
anti-inflammatory and immunosuppressive effects of HBO(2). We hope
that this will provide a basis for elucidating the mechanisms of
action and consequently pave the way for further controlled studies.
PMID: 19830133
===================
OK, this is the same thing as the lead article up top.
I just wanted both of them from different perspectives. :)
http://www.sciencedaily.com/releases/2009/10/091015123544.htm
In Shaping Our Immune Systems, Some 'Friendly' Bacteria May Play
Inordinate Role
ScienceDaily (Oct. 15, 2009) — Out of the trillions of "friendly"
bacteria -- representing hundreds of species -- that make our
intestines their home, new evidence in mice suggests that it may be a
very select few that shape our immune responses. The findings detailed
in two October 16th reports appearing in the journals Cell and
Immunity, both Cell Press publications, offer new insight into the
constant dialogue that goes on between intestinal microbes and the
immune system, and point to a remarkably big role for a class of
microbes known as segmented filamentous bacteria (SFB).
"It's the first example of a commensal bacteria that can induce
accumulation in the gut of a highly specific branch of the immune
system," said Dan Littman of the Howard Hughes Medical Institute and
the New York University School of Medicine, who led the study reported
in Cell. "We're headed into an exciting new area, and we hope more
pieces of how the microbial-host interaction contributes to health
will begin to fall into place."
"Our study provides the surprising result that among the hundreds of
bacterial species composing the gut microbiota -- only a very small
number, the prototype of which is SFB -- can efficiently stimulate the
post-natal physiologic maturation of the immune barrier," added
Valérie Gaboriau-Routhiau of INSERM in France, who led the Immunity
report. "A unique feature of SFB appears to be its capacity to
simultaneously stimulate a large spectrum of intestinal immune
responses -- innate and adaptive, pro-inflammatory and regulatory --
which complete and balance each other."
Notably, those SFBs stimulate particular types of helper T cells,
known as Th17 cells, the studies show.
In Littman's case, the findings by his group were something of an
accidental discovery. They were studying T cells in the intestine and
were getting some inconsistencies in their results. Those
inconsistencies could be traced to differences in the gut floras of
mice obtained from different sources, and specifically, they found, in
the presence or absence of SFB.
Introduction of SFB, but not other bacteria, stimulated the production
of Th17 cells in mice who were otherwise deficient in them, they show.
The bacteria also set in motion a pro-inflammatory gene program. That
SFB-induced immune response protected the mice from becoming ill with
an intestinal pathogen, supporting a role for the SFBs in setting up
the intestine's immunity barrier.
Gaboriau-Routhiau similarly found in studies of conventional and germ-
free mice that colonization of the gut induced a broad spectrum of pro-
inflammatory and T cell responses, including the emergence of Th17
cells. That occurred despite the fact that most bacteria, in
combination or on their own, didn't lead to such a reaction. Rather,
that function appeared limited to a restricted number of bacteria, her
team reports, the prototype of which is the SFB. All on its own, SFB
could largely recapitulate the coordinated maturation of T cell
responses normally induced by the whole mouse microbiota.
Gaboriau-Routhiau suspects that SFBs may have some special attributes
that explain their importance.
"For us, it was first a surprise to observe so little redundancy in
the role of commensal bacteria on stimulating immune responses,"
Gaboriau-Routhiau said. "One striking feature of SFB, which makes it
very different from the vast majority of the members of the
microbiota, is its capacity to adhere to epithelial cells notably in
the ileum, a property normally more the prerogative of pathogens." The
ileum is the final section of the small intestine and is distinguished
by many folds, giving it a very substantial surface area.
The findings also suggest how such commensal bacteria might sometimes
go from beneficial inhabitants, helping to fend off nasty bugs, to
ones that may tip the balance of the immune system toward the
development of inflammatory, autoimmune disease, such as Crohn's
disease, psoriasis and even arthritis, according to the researchers.
Indeed, the Th17 cells observed in the new studies have been noted in
recent years because of their importance in autoimmune diseases,
Littman explained. Animals with defects in those Th17 cells generally
don't develop autoimmune disease or develop disease that is less
severe, earlier studies showed.
"Th17 cells make cytokines that can be highly protective in the case
of infection," he said. "At the same time, in the wrong context or in
the wrong amount [they can lead to disease]. You need to have the
right balance."
Given the bacterial diversity found within our guts, the new results
show how much there still is to learn about this important aspect of
the immune system. While probiotic products on the market today don't
have the benefit of such a thorough understanding, says Littman, there
is little doubt that down the road we may be able to manipulate our
immune system in beneficial ways with microbes. Alternatively, he
said, some of the molecular products of those bacteria – particular
sugars or peptides, for instance – might ultimately serve as useful
therapies on their own
----------
http://www.sciencedaily.com/images/2009/10/091015123544-large.jpg
A little-known bacterial species called segmented filamentous
bacterium, or SFB, can activate the production of specialized immune
cells in mice. This scanning electron microscope image of an SFB
colony shows a mass of long hair-like filaments created when the
bacteria stay attached to each other after they divide. (Credit:
Ivaylo Ivanov and Dan Littman (NYU Langone Medical Center) and Doug
Wei (Carl Zeiss SMT, Inc.))
<sniP>
==============
randall...