PMID- 33122426 OWN - NLM STAT- MEDLINE DCOM- 20210121 LR - 20211012 IS - 1095-9203 (Electronic) IS - 0036-8075 (Linking) VI - 370 IP - 6519 DP - 2020 Nov 20 TI - Fetal mast cells mediate postnatal allergic responses dependent on maternal IgE. PG - 941-950 LID - 10.1126/science.aba0864 [doi] AB - Mast cells (MCs) are central effector cells in allergic reactions that are often mediated by immunoglobulin E (IgE). Allergies commonly start at an early age, and both MCs and IgE are detectable in fetuses. However, the origin of fetal IgE and whether fetal MCs can degranulate in response to IgE-dependent activation are presently unknown. Here, we show that human and mouse fetal MCs phenotypically mature through pregnancy and can be sensitized by maternal IgE. IgE crossed the placenta, dependent on the fetal neonatal Fc receptor (FcRN), and sensitized fetal MCs for allergen-specific degranulation. Both passive and active prenatal sensitization conferred allergen sensitivity, resulting in postnatal skin and airway inflammation after the first allergen encounter. We report a role for MCs within the developing fetus and demonstrate that fetal MCs may contribute to antigen-specific vertical transmission of allergic disease. CI - Copyright (c) 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. FAU - Msallam, Rasha AU - Msallam R AD - Singapore Immunology Network (SIgN), A*STAR, Singapore 138648, Singapore. FAU - Balla, Jozef AU - Balla J AUID- ORCID: 0000-0001-7164-4856 AD - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore. FAU - Rathore, Abhay P S AU - Rathore APS AUID- ORCID: 0000-0003-2039-2964 AD - Department of Pathology, Duke University Medical Center, Durham, NC 27705, USA. FAU - Kared, Hassen AU - Kared H AUID- ORCID: 0000-0002-8220-997X AD - Singapore Immunology Network (SIgN), A*STAR, Singapore 138648, Singapore. FAU - Malleret, Benoit AU - Malleret B AUID- ORCID: 0000-0001-9658-7528 AD - Singapore Immunology Network (SIgN), A*STAR, Singapore 138648, Singapore. AD - Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore. FAU - Saron, Wilfried A A AU - Saron WAA AUID- ORCID: 0000-0002-7974-5288 AD - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore. FAU - Liu, Zhaoyuan AU - Liu Z AUID- ORCID: 0000-0002-3117-0833 AD - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. FAU - Hang, Jing Wen AU - Hang JW AUID- ORCID: 0000-0001-9491-4492 AD - Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore. FAU - Dutertre, Charles Antoine AU - Dutertre CA AD - Singapore Immunology Network (SIgN), A*STAR, Singapore 138648, Singapore. AD - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore. FAU - Larbi, Anis AU - Larbi A AD - Singapore Immunology Network (SIgN), A*STAR, Singapore 138648, Singapore. FAU - Chan, Jerry K Y AU - Chan JKY AD - Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore 229899, Singapore. AD - Academic Clinical Program of Obstetrics and Gynaecology, Duke-NUS Medical School, Singapore 229899, Singapore. AD - Experimental Fetal Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. FAU - St John, Ashley L AU - St John AL AUID- ORCID: 0000-0001-5098-1044 AD - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore. Florent_Ginhoux@immunol.a-star.edu.sg ashley.st.john@duke-nus.edu.sg. AD - Department of Pathology, Duke University Medical Center, Durham, NC 27705, USA. AD - Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore. AD - SingHealth Duke-NUS Global Health Institute, Singapore 169857, Singapore. FAU - Ginhoux, Florent AU - Ginhoux F AUID- ORCID: 0000-0002-2857-7755 AD - Singapore Immunology Network (SIgN), A*STAR, Singapore 138648, Singapore. Florent_Ginhoux@immunol.a-star.edu.sg ashley.st.john@duke-nus.edu.sg. AD - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. AD - Translational Immunology Institute, SingHealth/Duke-NUS Academic Medical Centre, The Academia, Singapore 169856, Singapore. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201029 PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Allergens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Receptors, Fc) RN - 37341-29-0 (Immunoglobulin E) RN - TW3XAW0RCY (Fc receptor, neonatal) SB - IM CIN - Science. 2020 Nov 20;370(6519):907-908. PMID: 33214263 CIN - Nat Rev Immunol. 2021 Jan;21(1):2-3. PMID: 33257821 CIN - Allergy. 2021 Oct;76(10):3236-3237. PMID: 33840097 CIN - J Allergy Clin Immunol. 2021 Jul;148(1):76-77. PMID: 33872654 MH - Allergens/immunology MH - Ambrosia/immunology MH - Animals MH - Cell Degranulation/immunology MH - Female MH - Fetus/*immunology MH - Histocompatibility Antigens Class I/physiology MH - Humans MH - Hypersensitivity/*immunology MH - Immunoglobulin E/*immunology MH - Mast Cells/*immunology MH - Maternal-Fetal Exchange/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Placenta/immunology MH - Pregnancy MH - Receptors, Fc/physiology EDAT- 2020/10/31 06:00 MHDA- 2021/01/22 06:00 CRDT- 2020/10/30 05:45 PHST- 2019/11/03 00:00 [received] PHST- 2020/07/25 00:00 [revised] PHST- 2020/10/20 00:00 [accepted] PHST- 2020/10/31 06:00 [pubmed] PHST- 2021/01/22 06:00 [medline] PHST- 2020/10/30 05:45 [entrez] AID - science.aba0864 [pii] AID - 10.1126/science.aba0864 [doi] PST - ppublish SO - Science. 2020 Nov 20;370(6519):941-950. doi: 10.1126/science.aba0864. Epub 2020 Oct 29.