Non-cytotoxic Cardiac Innate Lymphoid Cells Are a Resident and Quiescent Type 2-Commited Population
Innate lymphoid cells (ILC) are a subset of leukocytes with lymphoid properties that lack antigen specific receptors. They can be stimulated by and exert their effect via specific cytokine axes, whereas Natural Killers (NK) cells are the only known cytotoxic member of this family. ILCs are considere...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2019-03-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00634/full |
id |
doaj-045793709dc24b8e88455b62d435752f |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
William Bracamonte-Baran Guobao Chen Xuezhou Hou Monica V. Talor Hee Sun Choi Giovanni Davogustto Heinrich Taegtmeyer Jungeun Sung David Joel Hackam David Nauen Daniela Čiháková Daniela Čiháková |
spellingShingle |
William Bracamonte-Baran Guobao Chen Xuezhou Hou Monica V. Talor Hee Sun Choi Giovanni Davogustto Heinrich Taegtmeyer Jungeun Sung David Joel Hackam David Nauen Daniela Čiháková Daniela Čiháková Non-cytotoxic Cardiac Innate Lymphoid Cells Are a Resident and Quiescent Type 2-Commited Population Frontiers in Immunology innate lymphoid cells IL-33 heart myocarditis myocardial infarction fibroblasts |
author_facet |
William Bracamonte-Baran Guobao Chen Xuezhou Hou Monica V. Talor Hee Sun Choi Giovanni Davogustto Heinrich Taegtmeyer Jungeun Sung David Joel Hackam David Nauen Daniela Čiháková Daniela Čiháková |
author_sort |
William Bracamonte-Baran |
title |
Non-cytotoxic Cardiac Innate Lymphoid Cells Are a Resident and Quiescent Type 2-Commited Population |
title_short |
Non-cytotoxic Cardiac Innate Lymphoid Cells Are a Resident and Quiescent Type 2-Commited Population |
title_full |
Non-cytotoxic Cardiac Innate Lymphoid Cells Are a Resident and Quiescent Type 2-Commited Population |
title_fullStr |
Non-cytotoxic Cardiac Innate Lymphoid Cells Are a Resident and Quiescent Type 2-Commited Population |
title_full_unstemmed |
Non-cytotoxic Cardiac Innate Lymphoid Cells Are a Resident and Quiescent Type 2-Commited Population |
title_sort |
non-cytotoxic cardiac innate lymphoid cells are a resident and quiescent type 2-commited population |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-03-01 |
description |
Innate lymphoid cells (ILC) are a subset of leukocytes with lymphoid properties that lack antigen specific receptors. They can be stimulated by and exert their effect via specific cytokine axes, whereas Natural Killers (NK) cells are the only known cytotoxic member of this family. ILCs are considered key in linking the innate and adaptive response in physiologic and pathologic environments. In this study, we investigated the properties of non-cytotoxic cardiac ILCs in physiologic, inflammatory, and ischemic conditions. We found that in healthy humans and mice, non-cytotoxic cardiac ILCs are predominantly a type 2-committed population with progenitor-like features, such as an absence of type-specific immunophenotype, intermediate GATA3 expression, and capacity to transiently express Pro-myelocytic Leukemia Zinc Finger protein (PLZF) upon activation. During myocarditis and ischemia, in both human and mice, cardiac ILCs differentiated into conventional ILC2s. We found that cardiac ILCs lack IL-25 receptor and cannot become inflammatory ILC2s. We found a strong correlation between IL-33 production in the heart and the ability of cardiac ILCs to become conventional ILC2s. The main producer of IL-33 was a subset of CD29+Sca-1+ cardiac fibroblasts. ILC2 expansion and fibroblast-derived IL-33 production were significantly increased in the heart in mouse models of infarction and myocarditis. Despite its progenitor-like status in healthy hearts, cardiac ILCs were unable to become ILC1 or ILC3 in vivo and in vitro. Using adoptive transfer and parabiosis, we demonstrated that the heart, unlike other organs such as lung, cannot be infiltrated by circulating ILCs in adulthood even during cardiac inflammation or ischemia. Thus, the ILC2s present during inflammatory conditions are derived from the heart-resident and quiescent steady-state population. Non-cytotoxic cardiac ILCs are a resident population of ILC2-commited cells, with undifferentiated progenitor-like features in steady-state conditions and an ability to expand and develop pro-inflammatory type 2 features during inflammation or ischemia. |
topic |
innate lymphoid cells IL-33 heart myocarditis myocardial infarction fibroblasts |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.00634/full |
work_keys_str_mv |
AT williambracamontebaran noncytotoxiccardiacinnatelymphoidcellsarearesidentandquiescenttype2commitedpopulation AT guobaochen noncytotoxiccardiacinnatelymphoidcellsarearesidentandquiescenttype2commitedpopulation AT xuezhouhou noncytotoxiccardiacinnatelymphoidcellsarearesidentandquiescenttype2commitedpopulation AT monicavtalor noncytotoxiccardiacinnatelymphoidcellsarearesidentandquiescenttype2commitedpopulation AT heesunchoi noncytotoxiccardiacinnatelymphoidcellsarearesidentandquiescenttype2commitedpopulation AT giovannidavogustto noncytotoxiccardiacinnatelymphoidcellsarearesidentandquiescenttype2commitedpopulation AT heinrichtaegtmeyer noncytotoxiccardiacinnatelymphoidcellsarearesidentandquiescenttype2commitedpopulation AT jungeunsung noncytotoxiccardiacinnatelymphoidcellsarearesidentandquiescenttype2commitedpopulation AT davidjoelhackam noncytotoxiccardiacinnatelymphoidcellsarearesidentandquiescenttype2commitedpopulation AT davidnauen noncytotoxiccardiacinnatelymphoidcellsarearesidentandquiescenttype2commitedpopulation AT danielacihakova noncytotoxiccardiacinnatelymphoidcellsarearesidentandquiescenttype2commitedpopulation AT danielacihakova noncytotoxiccardiacinnatelymphoidcellsarearesidentandquiescenttype2commitedpopulation |
_version_ |
1725084407676534784 |
spelling |
doaj-045793709dc24b8e88455b62d435752f2020-11-25T01:31:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00634428966Non-cytotoxic Cardiac Innate Lymphoid Cells Are a Resident and Quiescent Type 2-Commited PopulationWilliam Bracamonte-Baran0Guobao Chen1Xuezhou Hou2Monica V. Talor3Hee Sun Choi4Giovanni Davogustto5Heinrich Taegtmeyer6Jungeun Sung7David Joel Hackam8David Nauen9Daniela Čiháková10Daniela Čiháková11Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesW. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesDivision of Cardiology, Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX, United StatesDivision of Cardiology, Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX, United StatesSchool of Medicine, Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, United StatesDivision of General Pediatric Surgery, Johns Hopkins University and Bloomberg Children's Center, Johns Hopkins Hospital, Baltimore, MD, United StatesDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesW. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesInnate lymphoid cells (ILC) are a subset of leukocytes with lymphoid properties that lack antigen specific receptors. They can be stimulated by and exert their effect via specific cytokine axes, whereas Natural Killers (NK) cells are the only known cytotoxic member of this family. ILCs are considered key in linking the innate and adaptive response in physiologic and pathologic environments. In this study, we investigated the properties of non-cytotoxic cardiac ILCs in physiologic, inflammatory, and ischemic conditions. We found that in healthy humans and mice, non-cytotoxic cardiac ILCs are predominantly a type 2-committed population with progenitor-like features, such as an absence of type-specific immunophenotype, intermediate GATA3 expression, and capacity to transiently express Pro-myelocytic Leukemia Zinc Finger protein (PLZF) upon activation. During myocarditis and ischemia, in both human and mice, cardiac ILCs differentiated into conventional ILC2s. We found that cardiac ILCs lack IL-25 receptor and cannot become inflammatory ILC2s. We found a strong correlation between IL-33 production in the heart and the ability of cardiac ILCs to become conventional ILC2s. The main producer of IL-33 was a subset of CD29+Sca-1+ cardiac fibroblasts. ILC2 expansion and fibroblast-derived IL-33 production were significantly increased in the heart in mouse models of infarction and myocarditis. Despite its progenitor-like status in healthy hearts, cardiac ILCs were unable to become ILC1 or ILC3 in vivo and in vitro. Using adoptive transfer and parabiosis, we demonstrated that the heart, unlike other organs such as lung, cannot be infiltrated by circulating ILCs in adulthood even during cardiac inflammation or ischemia. Thus, the ILC2s present during inflammatory conditions are derived from the heart-resident and quiescent steady-state population. Non-cytotoxic cardiac ILCs are a resident population of ILC2-commited cells, with undifferentiated progenitor-like features in steady-state conditions and an ability to expand and develop pro-inflammatory type 2 features during inflammation or ischemia.https://www.frontiersin.org/article/10.3389/fimmu.2019.00634/fullinnate lymphoid cellsIL-33heartmyocarditismyocardial infarctionfibroblasts |