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Keeping the lid on a can of worms –

New insights into the function of basophilic granulocytes

Munich, 09/27/2010

Basophilic granulocytes (basophils) are the Ugly Ducklings of immunology. They are relatively rare and were largely ignored by researchers until quite recently. But these leukocytes (white blood cells) actually play an important role in the fight against infection, as a team of researchers led by LMU immunologist Dr David Vöhringer has just shown. For their experiments, the team first constructed a mouse strain that specifically lacks basophils . This model system allowed them to ask whether or not these leukocytes participate in various immune reactions. “Using this approach, we have been able to confirm some of the suspected functions of basophils, while ruling out others”, says Christian Schwartz, who made a major contribution to the new study. “It turns out that they are important for the prevention of recurrent infections by parasitic worms, but they also play a decisive role in the development of allergic dermatitis, a type of chronic inflammation of the skin.” The innovative mouse model promises to provide researchers with a much more detailed picture of the functions of basophils in the near future, and may lead to new therapies. (Immunity vol 33, pp 364-374, 24 September 2010)

The leukocyte population, which comprises the white cells found in the blood, is made up of several different cell types, which originate in the bone marrow. Basophils are the rarest of these, accounting for less than 2% of the total population, and their function has long remained unclear. However, there have been hints that they are involved in the development of allergic dermatitis, a type of chronic skin inflammation, and in the acute allergic hypersensitivity reaction known as anaphylaxis. The cells have also been linked to the so-called Th2 response of the immune system.

A team of investigators led by Privatdozent Dr David Vöhringer of the Institute of Immunology at LMU Munich has now developed a mouse model that, for the first time, allowed them to assess the significance of basophils for the execution of diverse immune responses. The researchers generated a mouse strain that expresses the Cre-recombinase under control of regulatory elements of a basophil-specific protease (Mcpt8) and observed that these mice failed to develop any basophils. The immunologists then used this system to explore the effects of this defect on the strain’s ability to mount various types of immune and allergic reactions.

“We found that these leukocytes are indeed associated with Type 2 immune responses, but are not strictly necessary for their induction“, reports Christian Schwartz. “Type 2 responses are defence reactions which require the participation of T helper cells of type 2, and the basophils appear important for protection against parasitic worms, particularly in cases of reinfection.“ The team also confirmed that basophilis contribute to the development of chronic allergic dermatitis, but are not involved in anaphylactic reactions. Anaphylaxis is an acute allergic reaction that can occur following contact with an allergen. It is characterized by rapid dilation of the blood vessels, with a consequent sudden decrease in blood pressure, which can lead to death due to acute heart failure.

The new mouse model should help immunologists to elucidate the roles of basophils in the regulation and execution of various types of immune response. ”We are already planning a number of follow-up projects”, says David Vöhringer. “First we want to dissect in detail the functions performed by this poorly understood cell type. Our findings, such as those that point to the involvement of these basophils in allergic reactions, could lead to the development of new treatment strategies for allergic conditions.“ (CA/suwe)

The study was supported by the award of an Emmy Noether Fellowship from the Deutsche Forschungsgemeinschaft and a Starting Grant from the European Research Council to David Vöhringer.

 

Publication:
Basophils Orchestrate Chronic Allergic Dermatitis and Protective Immunity against Helminths;
Caspar Ohnmacht, Christian Schwartz, Marc Panzer, Isabell Schiedewitz, Ronald Naumann, David Voehringer;
Immunity, vol 33, pp 364-374
24 September 2010
DOI: 10.1016/j.immuni.2010.08.011

Contact:
PD Dr David Vöhringer
Institute of Immunology
LMU Munich
Phone: +49 (0) 89/2180-75646
Fax: +49-(0)89-2180-9975646
E-mail: david.voehringer@med.uni-muenchen.de
Web: www.immunologie.med.uni-muenchen.de/research/ag_voehringer

 

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