PMID- 37438525
OWN - NLM
STAT- MEDLINE
DCOM- 20230823
LR  - 20240504
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 620
IP  - 7974
DP  - 2023 Aug
TI  - Mast cells link immune sensing to antigen-avoidance behaviour.
PG  - 634-642
LID - 10.1038/s41586-023-06188-0 [doi]
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 avoidance(1-3). Here, we show that antigen-specific 
      avoidance behaviour in inbred mice(4,5) 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.
CI  - (c) 2023. The Author(s).
FAU - Plum, Thomas
AU  - Plum T
AUID- ORCID: 0000-0002-7811-4476
AD  - Division for Cellular Immunology, German Cancer Research Center, Heidelberg, 
      Germany. t.plum@dkfz.de.
FAU - Binzberger, Rebecca
AU  - Binzberger R
AD  - Division for Cellular Immunology, German Cancer Research Center, Heidelberg, 
      Germany.
AD  - Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
FAU - Thiele, Robin
AU  - Thiele R
AD  - Division for Cellular Immunology, German Cancer Research Center, Heidelberg, 
      Germany.
AD  - Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
FAU - Shang, Fuwei
AU  - Shang F
AD  - Division for Cellular Immunology, German Cancer Research Center, Heidelberg, 
      Germany.
AD  - Faculty of Medicine, Heidelberg University, Heidelberg, Germany.
FAU - Postrach, Daniel
AU  - Postrach D
AD  - Division for Cellular Immunology, German Cancer Research Center, Heidelberg, 
      Germany.
AD  - Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
FAU - Fung, Candice
AU  - Fung C
AUID- ORCID: 0000-0002-4277-3664
AD  - Laboratory for Enteric NeuroScience Translational Research Center for 
      Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.
FAU - Fortea, Marina
AU  - Fortea M
AD  - Laboratory for Enteric NeuroScience Translational Research Center for 
      Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.
FAU - Stakenborg, Nathalie
AU  - Stakenborg N
AUID- ORCID: 0000-0002-6229-0045
AD  - Laboratory for Intestinal Neuroimmune Interactions, Department of Chronic 
      Diseases, Metabolism and Ageing, Translational Research Center for 
      Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.
FAU - Wang, Zheng
AU  - Wang Z
AD  - Laboratory for Intestinal Neuroimmune Interactions, Department of Chronic 
      Diseases, Metabolism and Ageing, Translational Research Center for 
      Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.
FAU - Tappe-Theodor, Anke
AU  - Tappe-Theodor A
AUID- ORCID: 0000-0002-9343-7580
AD  - Pharmacology Institute, Heidelberg University, Heidelberg, Germany.
FAU - Poth, Tanja
AU  - Poth T
AD  - Center for Model System and Comparative Pathology, Institute of Pathology, 
      Heidelberg University Hospital, Heidelberg, Germany.
FAU - MacLaren, Duncan A A
AU  - MacLaren DAA
AD  - Department of Clinical Neurobiology of the Medical Faculty of Heidelberg 
      University and German Cancer Research Center, Heidelberg, Germany.
FAU - Boeckxstaens, Guy
AU  - Boeckxstaens G
AUID- ORCID: 0000-0001-8267-5797
AD  - Laboratory for Intestinal Neuroimmune Interactions, Department of Chronic 
      Diseases, Metabolism and Ageing, Translational Research Center for 
      Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.
FAU - Kuner, Rohini
AU  - Kuner R
AUID- ORCID: 0000-0002-3333-9129
AD  - Pharmacology Institute, Heidelberg University, Heidelberg, Germany.
FAU - Pitzer, Claudia
AU  - Pitzer C
AUID- ORCID: 0000-0002-7663-1031
AD  - Interdisciplinary Neurobehavioral Core, Heidelberg University, Heidelberg, 
      Germany.
FAU - Monyer, Hannah
AU  - Monyer H
AD  - Department of Clinical Neurobiology of the Medical Faculty of Heidelberg 
      University and German Cancer Research Center, Heidelberg, Germany.
FAU - Xin, Cuiyan
AU  - Xin C
AD  - Division of Renal Medicine and Division of Engineering in Medicine, Department of 
      Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
FAU - Bonventre, Joseph V
AU  - Bonventre JV
AUID- ORCID: 0000-0001-7144-386X
AD  - Division of Renal Medicine and Division of Engineering in Medicine, Department of 
      Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
FAU - Tanaka, Satoshi
AU  - Tanaka S
AUID- ORCID: 0000-0002-3468-7694
AD  - Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto 
      Pharmaceutical University, Kyoto, Japan.
FAU - Voehringer, David
AU  - Voehringer D
AUID- ORCID: 0000-0001-6650-0639
AD  - Department of Infection Biology, University Hospital Erlangen and 
      Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
FAU - Vanden Berghe, Pieter
AU  - Vanden Berghe P
AUID- ORCID: 0000-0002-0009-2094
AD  - Laboratory for Enteric NeuroScience Translational Research Center for 
      Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.
FAU - Strid, Jessica
AU  - Strid J
AUID- ORCID: 0000-0003-3690-2201
AD  - Department of Immunology and Inflammation, Imperial College London, London, UK.
FAU - Feyerabend, Thorsten B
AU  - Feyerabend TB
AUID- ORCID: 0000-0002-1205-6568
AD  - Division for Cellular Immunology, German Cancer Research Center, Heidelberg, 
      Germany.
FAU - Rodewald, Hans-Reimer
AU  - Rodewald HR
AUID- ORCID: 0000-0002-1452-3828
AD  - Division for Cellular Immunology, German Cancer Research Center, Heidelberg, 
      Germany. hr.rodewald@dkfz.de.
LA  - eng
GR  - R01 DK072381/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20230712
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Allergens)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 0 (Cytokines)
RN  - 0 (Leukotrienes)
SB  - IM
CIN - Trends Immunol. 2023 Sep;44(9):665-667. PMID: 37586904
CIN - Immunity. 2023 Sep 12;56(9):1988-1990. PMID: 37703829
MH  - Animals
MH  - Mice
MH  - *Allergens/immunology
MH  - *Avoidance Learning/physiology
MH  - *Hypersensitivity/immunology
MH  - Immunoglobulin E/immunology
MH  - *Mast Cells/immunology
MH  - Stomach/immunology
MH  - Vagotomy
MH  - Immunity, Innate/immunology
MH  - Immunity, Mucosal/immunology
MH  - Th2 Cells/immunology
MH  - Cytokines/immunology
MH  - Leukotrienes/biosynthesis/immunology
MH  - Intestine, Small/immunology
PMC - PMC10432277
COIS- The authors declare no competing interests.
EDAT- 2023/07/13 01:06
MHDA- 2023/08/18 06:43
PMCR- 2023/07/12
CRDT- 2023/07/12 23:31
PHST- 2022/06/12 00:00 [received]
PHST- 2023/05/10 00:00 [accepted]
PHST- 2023/08/18 06:43 [medline]
PHST- 2023/07/13 01:06 [pubmed]
PHST- 2023/07/12 23:31 [entrez]
PHST- 2023/07/12 00:00 [pmc-release]
AID - 10.1038/s41586-023-06188-0 [pii]
AID - 6188 [pii]
AID - 10.1038/s41586-023-06188-0 [doi]
PST - ppublish
SO  - Nature. 2023 Aug;620(7974):634-642. doi: 10.1038/s41586-023-06188-0. Epub 2023 
      Jul 12.