Landscape of Mast Cell Populations Across Organs in Mice and Humans

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2023 Jul 18

PMID 37462672

Authors

Marie Tauber

Lilian Basso

Jeremy Martin

Luciana Bostan

Marlene Magalhaes Pinto

Guilhem R Thierry

Raissa Houmadi

Nadine Serhan

Alexia Loste

Camille Bleriot

Jasper B J Kamphuis

Mirjana Grujic

Lena Kjellen

Gunnar Pejler

Carle Paul

Xinzhong Dong

Stephen J Galli

Laurent L Reber

Florent Ginhoux

Marc Bajenoff

Rebecca Gentek

Nicolas Gaudenzio

Affiliations

Soon will be listed here.

Abstract

Mast cells (MCs) are tissue-resident immune cells that exhibit homeostatic and neuron-associated functions. Here, we combined whole-tissue imaging and single-cell RNA sequencing datasets to generate a pan-organ analysis of MCs in mice and humans at steady state. In mice, we identify two mutually exclusive MC populations, MrgprB2+ connective tissue-type MCs and MrgprB2neg mucosal-type MCs, with specific transcriptomic core signatures. While MrgprB2+ MCs develop in utero independently of the bone marrow, MrgprB2neg MCs develop after birth and are renewed by bone marrow progenitors. In humans, we unbiasedly identify seven MC subsets (MC1-7) distributed across 12 organs with different transcriptomic core signatures. MC1 are preferentially enriched in the bladder, MC2 in the lungs, and MC4, MC6, and MC7 in the skin. Conversely, MC3 and MC5 are shared by most organs but not skin. This comprehensive analysis offers valuable insights into the natural diversity of MC subtypes in both mice and humans.

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References

Gentek R, Ghigo C, Hoeffel G, Bulle M, Msallam R, Gautier G . Hemogenic Endothelial Fate Mapping Reveals Dual Developmental Origin of Mast Cells. Immunity. 2018; 48(6):1160-1171.e5. DOI: 10.1016/j.immuni.2018.04.025. View

Gurish M, Boyce J . Mast cells: ontogeny, homing, and recruitment of a unique innate effector cell. J Allergy Clin Immunol. 2006; 117(6):1285-91. DOI: 10.1016/j.jaci.2006.04.017. View

Gabanyi I, Muller P, Feighery L, Oliveira T, Costa-Pinto F, Mucida D . Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages. Cell. 2016; 164(3):378-91. PMC: 4733406. DOI: 10.1016/j.cell.2015.12.023. View

Galli S, Tsai M, Marichal T, Tchougounova E, Reber L, Pejler G . Approaches for analyzing the roles of mast cells and their proteases in vivo. Adv Immunol. 2015; 126:45-127. PMC: 4771191. DOI: 10.1016/bs.ai.2014.11.002. View

Lawrence C, Paterson Y, Wright S, Knight P, Miller H . Mouse mast cell protease-1 is required for the enteropathy induced by gastrointestinal helminth infection in the mouse. Gastroenterology. 2004; 127(1):155-65. DOI: 10.1053/j.gastro.2004.04.004. View

Scholten J, Hartmann K, Gerbaulet A, Krieg T, Muller W, Testa G . Mast cell-specific Cre/loxP-mediated recombination in vivo. Transgenic Res. 2007; 17(2):307-15. PMC: 2268725. DOI: 10.1007/s11248-007-9153-4. View

Cao J, Spielmann M, Qiu X, Huang X, Ibrahim D, Hill A . The single-cell transcriptional landscape of mammalian organogenesis. Nature. 2019; 566(7745):496-502. PMC: 6434952. DOI: 10.1038/s41586-019-0969-x. View

Schafer B, Piliponsky A, Oka T, Song C, Gerard N, Gerard C . Mast cell anaphylatoxin receptor expression can enhance IgE-dependent skin inflammation in mice. J Allergy Clin Immunol. 2012; 131(2):541-8.e1-9. PMC: 3597773. DOI: 10.1016/j.jaci.2012.05.009. View

Li X, Serebrisky D, Lee S, Huang C, Bardina L, Schofield B . A murine model of peanut anaphylaxis: T- and B-cell responses to a major peanut allergen mimic human responses. J Allergy Clin Immunol. 2000; 106(1 Pt 1):150-8. DOI: 10.1067/mai.2000.107395. View

10.

Knight P, Wright S, Lawrence C, Paterson Y, Miller H . Delayed expulsion of the nematode Trichinella spiralis in mice lacking the mucosal mast cell-specific granule chymase, mouse mast cell protease-1. J Exp Med. 2000; 192(12):1849-56. PMC: 2213497. DOI: 10.1084/jem.192.12.1849. View

11.

Aran D, Looney A, Liu L, Wu E, Fong V, Hsu A . Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat Immunol. 2019; 20(2):163-172. PMC: 6340744. DOI: 10.1038/s41590-018-0276-y. View

12.

Basso L, Serhan N, Tauber M, Gaudenzio N . Peripheral neurons: Master regulators of skin and mucosal immune response. Eur J Immunol. 2019; 49(11):1984-1997. DOI: 10.1002/eji.201848027. View

13.

Schwarzer M, Hermanova P, Srutkova D, Golias J, Hudcovic T, Zwicker C . Germ-Free Mice Exhibit Mast Cells With Impaired Functionality and Gut Homing and Do Not Develop Food Allergy. Front Immunol. 2019; 10:205. PMC: 6379318. DOI: 10.3389/fimmu.2019.00205. View

14.

Meixiong J, Basso L, Dong X, Gaudenzio N . Nociceptor-Mast Cell Sensory Clusters as Regulators of Skin Homeostasis. Trends Neurosci. 2020; 43(3):130-132. DOI: 10.1016/j.tins.2020.01.001. View

15.

Boyce J . Mast cells can be commandeered for staphylococcal pathogenicity in patients with chronic rhinosinusitis with nasal polyposis. J Allergy Clin Immunol. 2019; 145(1):103-104. DOI: 10.1016/j.jaci.2019.11.006. View

16.

Nakano N, Kitaura J . Mucosal Mast Cells as Key Effector Cells in Food Allergies. Cells. 2022; 11(3). PMC: 8834119. DOI: 10.3390/cells11030329. View

17.

Roy S, Chompunud Na Ayudhya C, Thapaliya M, Deepak V, Ali H . Multifaceted MRGPRX2: New insight into the role of mast cells in health and disease. J Allergy Clin Immunol. 2021; 148(2):293-308. PMC: 8355064. DOI: 10.1016/j.jaci.2021.03.049. View

18.

Scott C, Zheng F, De Baetselier P, Martens L, Saeys Y, De Prijck S . Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells. Nat Commun. 2016; 7:10321. PMC: 4737801. DOI: 10.1038/ncomms10321. View

19.

McNeil B, Pundir P, Meeker S, Han L, Undem B, Kulka M . Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2014; 519(7542):237-41. PMC: 4359082. DOI: 10.1038/nature14022. View

20.

De Lisle R, Meldi L, Roach E, Flynn M, Sewell R . Mast cells and gastrointestinal dysmotility in the cystic fibrosis mouse. PLoS One. 2009; 4(1):e4283. PMC: 2627938. DOI: 10.1371/journal.pone.0004283. View