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.
In addition to Artis and Siracusa, co-authors are Steven A. Saenz, David A. Hill, Brian S. Kim, Travis A. Doering, E. John Wherry, and Taku Kambayashi, all from Penn, as well as Mark B. Headley and Steven F. Ziegler, Benaroya Research Institute, University of Washington School of Medicine; Heidi K. Jessup, Lori Siegel and Michael R. Comeau, Amgen Inc., Seattle; Emily C. Dudek, Antonella Cianferoni, & Jonathan M. Spergel, Children's Hospital of Philadelphia; and Masato Kubo, RIKEN Yokohama Institute, Tokyo University of Science.
The research was supported by the National Institutes of Health National Institute of Allergy and Infectious Diseases and the Burroughs Wellcome Fund.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.
Penn's Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools and among the top 10 schools for primary care.
The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.
Karen Kreeger | EurekAlert!
Why might reading make myopic?
18.07.2018 | Universitätsklinikum Tübingen
Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
18.07.2018 | Life Sciences
18.07.2018 | Materials Sciences
18.07.2018 | Health and Medicine