Research: (mouse) Scientists Unmask Mysterious Cells As Key 'Border Patrol Agents' In The Intestine
zumone2002
Scientists Unmask Mysterious Cells As Key 'Border Patrol Agents' In
The Intestine
10 May 2011
Researchers at UT Southwestern Medical Center have uncovered new clues
about how the intestine maintains friendly relations with the 100
trillion symbiotic bacteria that normally live in the digestive tract.
Their latest findings, available online today and in a future edition
of the Proceedings of the National Academy of Sciences, suggest that a
once enigmatic cell population which lurks in the intestinal lining is
essential for preventing friendly bacteria from invading into deeper
tissue where they can cause debilitating conditions like inflammatory
bowel disease (IBD).
"Possible new therapies for IBD could be devised by learning how to
boost the antibacterial functions of this particular group of cells,"
said Dr. Lora Hooper, associate professor of immunology and senior
author of the study.
"The findings also might help researchers better understand how
probiotics mixtures of beneficial bacteria that are added to food
products boost the immune system."
The human intestine is home to a staggering number of bacteria. These
microorganisms are put to good use as metabolic workhorses that help
to liberate nutrients from the diet for our uptake and use.
While most healthy people have a friendly relationship with their gut
microbes, this relationship turns sour in patients battling IBD.
People suffering from the disease frequently have more bacteria that
adhere to or invade their gut lining. When their immune system mounts
an attack on these microbial invaders, they can develop painful ulcers
and bloody diarrhea.
For this study, researchers studied mice genetically engineered to
lack a mysterious immune cell called a gamma deltaintraepithelial
lymphocyte (γδ IEL). This specialized T cell is found at body surfaces
such as the skin and the gastrointestinal tract, where it insinuates
itself between the epithelial cells that line these surfaces. These
cells make up a large proportion of the body's T cells, but their
exact function had been unclear.
"Our findings suggest that a major function of these T cells is to
patrol intestinal borders, sensing when microorganisms have invaded
the epithelial cells lining the intestine," said Dr. Hooper, who is
also an investigator for the Howard Hughes Medical Institute at UT
Southwestern. "When this happens, these T cells swing into action,
making antibiotic proteins that kill the rogue bacteria and prevent
their entry into deeper tissue."
The researchers also found IEL cells play an important role in
preventing intestinal pathogens such as Salmonella bacteria from
spreading to deeper tissues.
"These T cells manifest their importance in the first three to four
hours after the pathogen is encountered. This suggests that their
primary responsibility may be to 'hold down the fort' until other
immune cells can be recruited as backup," Dr. Hooper said.
--
Luke
Kofi
Flow cytometry of intestinal intraepithelial lymphocytes in celiac
disease.
Leon F.
Clinical Development, Alba Therapeutics, 800 W. Baltimore St, Suite 400,
Baltimore, MD 21201, USA.
This article reviews the multiple uses of flow cytometry in the
diagnosis, monitoring and research of celiac disease, the most prevalent
chronic autoimmune gastrointestinal disease. The phenotyping of
intraepithelial lymphocytes (IELs) is of clinical relevance in the
diagnosis of the disease given the characteristic features of elevated
CD3+ IELs (alphabeta and gammadelta TcR) and the decrease in CD3- IELs.
IEL biomarkers are also useful in the assessment of the response to the
gluten-free diet and, importantly, in the diagnosis of the severe
complications of celiac disease: refractory celiac disease and
enteropathy-associated T-cell lymphoma. Novel applications of flow
cytometry for the detection of anti-transglutaminase antibodies (a
validated biomarker of celiac disease) and of gluten (the triggering
antigen of the autoimmune process) are also discussed. The assessment of
diagnostic and prognostic biomarkers by flow cytometry in celiac disease
is performed routinely in a growing number of centers and it is an
example of the versatility of this technique and its applicability to
the research and clinical study of solid tissues. Copyright (c) 2010
Elsevier B.V. All rights reserved.
Publication Types:
* Review
PMID: 20833175
Dig Dis Sci. 2011 Jan 8
Dynamics of Non-conventional Intraepithelial Lymphocytes-NK, NKT, and
gammadelta T-in Celiac Disease: Relationship with Age, Diet, and
Histopathology.
Calleja S, Vivas S, Santiuste M, Arias L, Hernando M, Nistal E,
Casqueiro J, Ruiz de Morales JG.
Department of Immunology, Complejo Hospitalario Universitario de Leon,
Altos de Nava s/n, 24080, Leon, Spain.
BACKGROUND: Intraepithelial lymphocytes (IEL) are a heterogeneous
population of lymphocytes raised in celiac disease (CD), whose role in
CD pathogenesis remains to be defined. AIMS: To investigate how the age
of diagnosis, diet, and the severity of the histological lesions are
related to the changes observed in unconventional IEL populations.
METHODS: Prospective analysis of 101 confirmed celiac patients from a
single center, including 66 at diagnosis (45 children, 21 adults) and
112 non-celiac controls (12 children, 100 adults). IEL from duodenal
biopsies were studied by six-color flow cytometry. The results were
analyzed in relationship with age, diet (gluten intake), and
histopathology (Marsh type). RESULTS: In comparison with respective age
controls, both children and adult patients showed duodenal
intraepithelial lymphocytosis with significant differences in every
single non-conventional IEL population: CD3+ TCR gammadelta, NK (CD3-,
CD16+, CD56+), NKT (CD3+, CD161+, CD56+), and iNKT (CD3+ Valpha24) (P <
0.001 for all). Gluten intake was not only directly associated with
severe atrophy, but also with decreased percentages of NK (P = 0.02),
NKT (P = 0.003), and iNKT (P = 0.03). Changes in iNKT and gammadelta IEL
were more marked in celiac children compared with celiac adults (P =
0.02 and 0.01, respectively). In contrast, increased CD3+ TCR gammadelta
were diet- and Marsh grade-independent. CONCLUSIONS: The typical
phenotypical profile of intraepithelial lymphocytosis in untreated
pediatric and adult celiacs consists of increased CD3+ TCR gammadelta
populations with decreased NK, NKT, and iNKT cells. NK, NKT, and iNKT
IEL, but not gammadelta IEL, are dynamic populations associated with
diet, age, and histopathology.
PMID: 21221796
Immunity. 2010 Nov 24;33(5):791-803. Epub 2010 Nov 11.
Comment in:
* Nat Rev Immunol. 2011 Jan;11(1):6.
T regulatory cells maintain intestinal homeostasis by suppressing
gammadelta T cells.
Park SG, Mathur R, Long M, Hosh N, Hao L, Hayden MS, Ghosh S.
Department of Microbiology & Immunology, Columbia University, College of
Physicians & Surgeons, New York, NY 10032, USA.
Immune tolerance against enteric commensal bacteria is important for
preventing intestinal inflammation. Deletion of
phosphoinositide-dependent protein kinase 1 (Pdk1) in T cells via
Cd4-Cre induced chronic inflammation of the intestine despite the
importance of PDK1 in T cell activation. Analysis of colonic
intraepithelial lymphocytes of PDK1-deficient mice revealed markedly
increased CD8alpha(+) T cell receptor (TCR)gammadelta(+) T cells,
including an interleukin-17 (IL-17)-expressing population.
TCRgammadelta(+) T cells were responsible for the inflammatory colitis
as shown by the fact that deletion of Tcrd abolished spontaneous colitis
in the PDK1-deficient mice. This dysregulation of intestinal
TCRgammadelta(+) T cells was attributable to a reduction in the number
and functional capacity of PDK1-deficient T regulatory (Treg) cells.
Adoptive transfer of wild-type Treg cells abrogated the spontaneous
activation and proliferation of intestinal TCRgammadelta(+) T cells
observed in PDK1-deficient mice and prevented the development of
colitis. Therefore, suppression of intestinal TCRgammadelta(+) T cells
by Treg cells maintains enteric immune tolerance. Copyright (c) 2010
Elsevier Inc. All rights reserved.
Publication Types:
* Research Support, N.I.H., Extramural
PMID: 21074460
In article
<fe4d5589-b8bc-43eb...@gu8g2000vbb.googlegroups.com>,
zumone2002 <zumon...@yahoo.com> wrote:
> lymphocyte (ăä IEL). This specialized T cell is found at body surfaces