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@ARTICLE{Plum:277476,
author = {T. Plum$^*$ and R. Binzberger$^*$ and R. Thiele$^*$ and F.
Shang$^*$ and D. Postrach$^*$ and C. Fung and M. Fortea and
N. Stakenborg and Z. Wang and A. Tappe-Theodor and T. Poth
and D. MacLaren$^*$ and G. Boeckxstaens and R. Kuner and C.
Pitzer and H. Monyer$^*$ and C. Xin and J. V. Bonventre and
S. Tanaka and D. Voehringer and P. V. Berghe and J. Strid
and T. Feyerabend$^*$ and H.-R. Rodewald$^*$},
title = {{M}ast cells link immune sensing to antigen-avoidance
behaviour.},
journal = {Nature},
volume = {620},
number = {7974},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2023-01397},
pages = {634-642},
year = {2023},
note = {#EA:D110#LA:D110# / 2023 Aug;620(7974):634-642},
abstract = {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.},
cin = {D110 / A230},
ddc = {500},
cid = {I:(DE-He78)D110-20160331 / I:(DE-He78)A230-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37438525},
doi = {10.1038/s41586-023-06188-0},
url = {https://inrepo02.dkfz.de/record/277476},
}