Researchers identify a target that could combat allergies of early childhood
August 14, 2011 in Medical research
Allergic inflammation in the mouse lung. Activated airway epithelial cells (green) and alternatively activated macrophages (red) are visualized by immuno-fluorescent staining of histologic sections. Credit: Meera Nair, PhD Mark Siracusa, PhD and David Artis, PhD, Perelman School of Medicine, University of Pennsylvania
A pandemic of ailments called the "allergic march" -- the gradual acquisition of overlapping allergic diseases that commonly begins in early childhood -- has frustrated both parents and physicians. For the last three decades, an explosion of eczema, food allergies, hay fever, and asthma have afflicted children in the United States, the European Union, and many other countries.
What causes the march and how to derail it has remained elusive. Now, in this week's Nature, David Artis, PhD, an associate professor of Microbiology at the Perelman School of Medicine at the University of Pennsylvania, and a team of collaborating international scientists, identified that expression of the protein TSLP may influence susceptibility to multiple allergic diseases by regulating the maturation of basophils, an uncommon type of white blood cell. Specifically, TSLP elicits the maturation of a population of distinct basophils that promotes allergic inflammation.
"A fundamental question regarding the allergic march is if a child has eczema, for example, which is associated with TSLP production in skin cells, why would some of those children subsequently be more susceptible to other allergic diseases at different sites of the body such as the gut or the lung?" asks Artis. "Although we have known that TSLP is associated with allergic diseases for many years, how this biological messenger might influence multiple allergic diseases has been a puzzle."
The origins of the present study lie in previous reports that showed that different versions of the gene encoding TSLP, an inflammation-producing cytokine, are associated with increased susceptibility to multiple allergic disorders, and that exaggerated TSLP production is associated with asthma, eczema, and food allergies in children. Together, these studies indicate that TSLP could be a critical regulator of multiple cytokine-associated allergic inflammatory diseases.
In this new report, mice overexpressing TSLP developed allergic inflammation in their lungs, skin, and gut that was associated with very high levels of basophils. "The critical findings are that TSLP appears to activate the development and maturation of early-stage basophils in the bone marrow and that TSLP elicits a distinct type of basophil," explains first author Mark Siracusa, PhD, a Ruth L. Kirschstein National Research Service Fellow in the Artis lab. Based on these findings, the researchers speculate that this basophil maturation could promote allergic reactions at multiple tissue sites.
To translate these findings to patient populations, Artis and colleagues teamed up with a group of pediatricians at the Children's Hospital of Philadelphia to examine basophil responses in children that suffer from the food allergy-associated disease, eosinophilic esophagitis, which causes inflammation of the esophagus. Previous studies have shown that TSLP is overexpressed in food allergy patients. The team showed in the Nature paper that in children with food allergies basophils exhibited a different molecular make-up compared to non-allergy patients.
"It's promising that after more than 130 years since basophils were first discovered by Paul Ehrlich in Germany, we are still finding out new things about this cell population that could help in the design of new drugs to prevent or better fight allergic diseases," concludes Artis.
With more than 50 percent of Americans estimated to suffer from at least one allergic disease, says Artis, the team is hoping that targeting TSLP and basophils may offer new therapies for multiple allergic diseases.
Provided by
University of Pennsylvania School of Medicine
-
Food allergy-related disorder linked to master allergy gene
Mar 07, 2010 |
not rated yet |
0
-
Identified: Switch that turns on allergic disease in people
Jan 20, 2010 |
not rated yet |
0
-
Protein fuels inflammation in pancreatic and breast tumors
Feb 21, 2011 |
not rated yet |
0
-
Childhood eczema and hay fever leads to adult allergic asthma
Apr 15, 2011 |
not rated yet |
0
-
Novel study finds proton channels inhibit the release of histamine during allergic reactions
Jul 29, 2008 |
not rated yet |
0
-
Of mice and mental models: Neuroscientific implications of risk-optimized behavior in the mouse
11 hours ago |
not rated yet |
0
-
Limits to growth: Scientists identify key metastasis-enabling enzyme
May 22, 2012 |
5 / 5 (3) |
0
-
Seeing is as seeing does: Spatially-structured retinal input in early development of cortical maps
Apr 26, 2012 |
5 / 5 (4) |
1
-
Dreamless nights: Brain activity during nonrapid eye movement sleep
Apr 09, 2012 |
4.4 / 5 (12) |
0
-
Take your time: Neurobiology sheds light on the superiority of spaced vs. massed learning
Mar 28, 2012 |
4.5 / 5 (21) |
3
-
A question about drug tolerance
May 23, 2012
-
Poor nutrition leading to overeating?
May 23, 2012
-
Math and dyslexia?
May 21, 2012
-
portable metabolism meter?
May 21, 2012
-
Rare medical conditions on 20/20 tonight
May 18, 2012
-
"Good" Cholesterol in Doubt
May 17, 2012
- More from Physics Forums - Medical Sciences
More news stories
Implantable pain disk may help those with cancer
An estimated 3.5 million cancer patients around the globe are in severe pain from their disease, but many get no relief.
Medical research
9 hours ago |
not rated yet |
0
|
Energy levels link sleep control mechanisms
Sleep, or lack of it, can determine level of cognitive performance which is linked with accidents as well as increased risk of serious health problems. Links between cell energy levels, gene transcription ...
Medical research
11 hours ago |
not rated yet |
0
Researchers identify key brain cell in antidepressant action
(Medical Xpress) -- Antidepressant medications such as Prozac have helped improve mood and lessen anxiety in millions of people with major depression. But scientists know surprisingly little about how these drugs work.
Medical research
11 hours ago |
4 / 5 (1) |
0
|
Rockefeller scientists pioneer new method to determine mechanisms of drug action
(Medical Xpress) -- Knowing that a drug works is great. Knowing how it works is a luxury. And until now, determining a drugs mechanism of action has been a tedious and difficult process for scientists.
Medical research
11 hours ago |
not rated yet |
0
|
Like curry? New biological role identified for compound used in ancient medicine
Scientists have just identified a new reason why some curry dishes, made with spices humans have used for thousands of years, might be good for you.
Medical research
19 hours ago |
4.3 / 5 (9) |
2
|
Tongue analysis software uses ancient Chinese medicine to warn of disease
For 5,000 years, the Chinese have used a system of medicine based on the flow and balance of positive and negative energies in the body. In this system, the appearance of the tongue is one of the measures used to classify ...
Of mice and mental models: Neuroscientific implications of risk-optimized behavior in the mouse
(Medical Xpress) -- Regardless of an organism’s biological complexity, every encephalized animal continuously makes under-informed behavioral choices that can have serious consequences. Despite its ubiquity, ...
Cancer may require simpler genetic mutations than previously thought
Chromosomal deletions in DNA often involve just one of two gene copies inherited from either parent. But scientists haven't known how a deletion in one gene from one parent, called a "hemizygous" deletion, can contribute ...
Skp2 activates cancer-promoting, glucose-processing Akt
HER2 and its epidermal growth factor receptor cousins mobilize a specialized protein to activate a major player in cancer development and sugar metabolism, scientists report in the May 25 issue of Cell.
Early physical therapist treatment associated with reduced risk of healthcare utilization and reduced overall healthcare
A new study published in Spine shows that early treatment by a physical therapist for low back pain (LBP), as compared to delayed treatment, was associated with reduced risk of subsequent healthcare utilization and lower ...
Inherited DNA change explains overactive leukemia gene
A small inherited change in DNA is largely responsible for overactivating a gene linked to poor treatment response in people with acute leukemia.