TY  - JOUR
AU  - Plum, Thomas
AU  - Binzberger, Rebecca
AU  - Thiele, Robin
AU  - Shang, Fuwei
AU  - Postrach, Daniel
AU  - Fung, Candice
AU  - Fortea, Marina
AU  - Stakenborg, Nathalie
AU  - Wang, Zheng
AU  - Tappe-Theodor, Anke
AU  - Poth, Tanja
AU  - MacLaren, Duncan
AU  - Boeckxstaens, Guy
AU  - Kuner, Rohini
AU  - Pitzer, Claudia
AU  - Monyer, Hannah
AU  - Xin, Cuiyan
AU  - Bonventre, Joseph V
AU  - Tanaka, Satoshi
AU  - Voehringer, David
AU  - Berghe, Pieter Vanden
AU  - Strid, Jessica
AU  - Feyerabend, Thorsten
AU  - Rodewald, Hans-Reimer
TI  - Mast cells link immune sensing to antigen-avoidance behaviour.
JO  - Nature 
VL  - 620
IS  - 7974
SN  - 0028-0836
CY  - London [u.a.]
PB  - Nature Publ. Group
M1  - DKFZ-2023-01397
SP  - 634-642
PY  - 2023
N1  - #EA:D110#LA:D110# / 2023 Aug;620(7974):634-642
AB  - The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with immunoglobulin E (IgE), promote allergic diseases. Allergic symptoms may, however, facilitate expulsion of allergens, toxins and parasites and trigger future antigen avoidance1-3. Here, we show that antigen-specific avoidance behaviour in inbred mice4,5 is critically dependent on mast cells; hence, we identify the immunological sensor cell linking antigen recognition to avoidance behaviour. Avoidance prevented antigen-driven adaptive, innate and mucosal immune activation and inflammation in the stomach and small intestine. Avoidance was IgE dependent, promoted by Th2 cytokines in the immunization phase and by IgE in the execution phase. Mucosal mast cells lining the stomach and small intestine rapidly sensed antigen ingestion. We interrogated potential signalling routes between mast cells and the brain using mutant mice, pharmacological inhibition, neural activity recordings and vagotomy. Inhibition of leukotriene synthesis impaired avoidance, but overall no single pathway interruption completely abrogated avoidance, indicating complex regulation. Collectively, the stage for antigen avoidance is set when adaptive immunity equips mast cells with IgE as a telltale of past immune responses. On subsequent antigen ingestion, mast cells signal termination of antigen intake. Prevention of immunopathology-causing, continuous and futile responses against per se innocuous antigens or of repeated ingestion of toxins through mast-cell-mediated antigen-avoidance behaviour may be an important arm of immunity.
LB  - PUB:(DE-HGF)16
C6  - pmid:37438525
DO  - DOI:10.1038/s41586-023-06188-0
UR  - https://inrepo02.dkfz.de/record/277476
ER  -