MSGID: 1:317/3 64af7dfa   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Mast cells as a sensor: Enigmatic immune cells help us avoid harmful   
   allergens    
      
     Date:   
         July 12, 2023   
     Source:   
         German Cancer Research Center (Deutsches Krebsforschungszentrum,   
         DKFZ)   
     Summary:   
         The function of mast cells, which are part of the immune system,   
         is still a mystery. Scientists have now shown in mice: mast cells   
         function as a sensor that signals the animals to avoid antigens,   
         including harmful allergens, and thereby protect themselves from   
         health-threatening inflammatory reactions.   
      
      
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   The function of mast cells, which are part of the immune system, is   
   still a mystery. Scientists at the German Cancer Research Center (DKFZ)   
   have now shown in mice: mast cells function as a sensor that signals   
   the animals to avoid antigens, including harmful allergens, and thereby   
   protect themselves from health-threatening inflammatory reactions. The   
   findings were published in the journal Nature.   
      
   Mast cells are found primarily in tissues that separate the outside and   
   inside worlds of the body, such as the epithelia of the gastrointestinal   
   tract and lungs. Within the tissues, mast cells often reside near nerve   
   endings. Mast cells are well known to persons suffering from allergies   
   because they secrete messenger substances such as histamine, which cause   
   annoying to health- threatening allergic symptoms. These symptoms occur   
   when mast cells are activated by IgE class antibodies during repeated   
   antigen contact.   
      
   "Why mast cells and IgE exist at all has not yet been conclusively   
   explained," says Hans-Reimer Rodewald. The DKFZ immunologist and his team   
   have now been able to show for the first time in mice, in a combination of   
   behavioral experiments and immunological studies, that mast cells act like   
   a sensor that helps to avoid contact with allergens No antigen avoidance   
   without mast cells and IgE The DKFZ researchers immunized mice with   
   the allergen ovalbumin, a protein component of chicken egg white. They   
   then gave the animals the free choice of preferring either normal or   
   egg white-containing drinking water. Immunized animals avoided the egg   
   white-enriched water, while their non-immunized conspecifics clearly   
   preferred it. A large proportion of the immunized animals avoided the   
   egg white-containing water already one day after immunization, some mice   
   even after the first sip.   
      
   However, when the scientists performed this behavioral test with mice that   
   genetically lack mast cells, both immunized and non-immunized animals   
   preferred the egg white-containing water. Mice genetically unable to   
   produce IgE also showed no avoidance behavior. Thus, both components --   
   mast cells and IgE - - are responsible for antigen avoidance.   
      
   When the immunized mice had no choice because the egg white solution was   
   instilled in them, the animals developed inflammation in the stomach and   
   small intestine. "The avoidance behavior mediated by mast cells apparently   
   protects the animals from harmful immune reactions," explains Thomas Plum,   
   one of the first authors.   
      
   How do mast cells "talk" to the brain?  An important open question for   
   the scientists was now: How can mast cells, as a component of the immune   
   system, influence behavior? In what ways do immune cells "talk" to the   
   brain? The scientists examined a variety of biologically active substances   
   released by mast cells. These include leukotrienes, pro- inflammatory   
   messengers known to activate sensory nerves. If the researchers blocked   
   leukotriene synthesis, the immunized mice no longer showed the same   
   consequence in avoiding egg white. Leukotrienes therefore appear to be   
   at least partly involved in avoidance behavior. Further immunological and   
   neurobiological experiments are needed in the future to identify the nerve   
   connections through which the mast cell signal is reported to the brain.   
      
   "In the intestine, lungs or skin, immune reactions against non-infectious   
   antigens can occur as a result of so-called barrier disorders,   
   permeability of the tissues from the outside to the inside. In the case   
   of allergy, we call such antigens allergens. Whether these substances are   
   dangerous or not, it is important for the organism to avoid their further   
   intake in order to prevent inflammatory diseases. This is an evolutionary   
   advantage and finally a conclusive explanation of the physiological role   
   of mast cells and IgE," Rodewald summarizes the results.   
      
   Whether mast cells also contribute to the avoidance of harmful antigens   
   in humans must be addressed in further studies.   
      
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   Materials provided by German_Cancer_Research_Center_(Deutsches   
   Krebsforschungszentrum,_DKFZ). Note: Content may be edited for style   
   and length.   
      
      
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   Journal Reference:   
      1. Thomas Plum, Rebecca Binzberger, Robin Thiele, Fuwei Shang, Daniel   
         Postrach, Candice Fung, Marina Fortea, Nathalie Stakenborg, Zheng   
         Wang, Anke Tappe-Theodor, Tanja Poth, Duncan A. A. MacLaren,   
         Guy Boeckxstaens, Rohini Kuner, Claudia Pitzer, Hannah Monyer,   
         Cuiyan Xin, Joseph V.   
      
         Bonventre, Satoshi Tanaka, David Voehringer, Pieter Vanden Berghe,   
         Jessica Strid, Thorsten B. Feyerabend, Hans-Reimer Rodewald. Mast   
         cells link immune sensing to antigen-avoidance behaviour. Nature,   
         2023; DOI: 10.1038/s41586-023-06188-0   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/07/230712124624.htm   
      
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