For the first time, researchers from the University of Pittsburgh School of Medicine have identified genetic components of dendritic cells that are key to asthma and allergy-related immune response malfunction. Targeting these elements could result in more effective drugs to treat allergic disorders and asthma, according to a study reported in the May edition of the journal Nature Medicine.
Dendritic cells are vital to immune response in that they recognize, capture and introduce threatening organisms to T lymphocytes¯other immune cells that secrete potent proteins called cytokines that surround and destroy the invaders. However, the Pittsburgh team’s study goes further to illuminate a pathway that allergens use to act directly on dendritic cells to propel differentiation into the T lymphocytes that fight back.
“We now have identified a molecule, c-Kit, that is central to the process of allergic response,” said Anuradha Ray, Ph.D., co-corresponding author and professor of medicine and immunology in the Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine. “We show that genes encoding for c-Kit and the cytokine interleukin 6 (IL-6) are significantly activated when allergens are present, but c-Kit is the very first molecule that gets triggered.”
Interactions between viruses and bacteria and molecular steps that initiate the immune defense have remained largely unknown. Using cells cultured from c-Kit mutant mice, Dr. Ray, her husband and co-corresponding author Prabir Ray, Ph.D., and their colleagues studied molecular reactions to assaults by cholera toxin and a standard allergen, house dust mites. In addition to c-Kit and IL-6, they found effects on stem cell factor and Jagged-2¯immune system molecules that are parts of the activation process.
“We have known the T-cell side of the story for many years, and we know that dendritic cells are important, but what we did not know was how the dendritic cell does what it does,” said Dr. Prabir Ray. “Therapy directed against c-Kit specifically on dendritic cells using compounds coupled to c-Kit inhibitors such as Gleevec, a drug that is already FDA-approved and used in cancer treatment, may alleviate allergic diseases and, potentially, inflammatory bowel disease.”
The Pittsburgh team incubated dendritic cells with cholera toxin and house dust mite allergens, finding that both substances induced significant secretion of c-Kit and IL-6, initial steps in a cascade resulting in the activation of T helper cells.
“Dual upregulation of c-Kit and stem cell factor has been noted in some cancers, such as small cell lung cancer. IL-6 has been associated with cancers such as multiple myeloma,” said Dr. Anuradha Ray. “Collectively, similar approaches to inhibit c-Kit, in addition to Gleevec or other inhibiting compounds could alleviate multiple cancers.”
Michele Baum | EurekAlert!
Fish recognize their prey by electric colors
13.11.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
The dawn of a new era for genebanks - molecular characterisation of an entire genebank collection
13.11.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly
The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
13.11.2018 | Life Sciences
13.11.2018 | Life Sciences
13.11.2018 | Awards Funding