title: Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency.
abstract: Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells that represent a broader category of NK cells in mucosal and non-mucosal pathological tissues. In addition, we have revealed the expression of phenotypic molecules that have not been previously described for ILCs. Our analysis shows that human ILCs are highly heterogeneous cell types between individuals and tissues. It also provides a global, comprehensive, and detailed description of ILC heterogeneity in humans across patients and tissues.
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), 138648 Singapore. Electronic address: yannick_simoni@immunol.a-star.edu.sg.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Simoni
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), 138648 Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Fehlings
authors.affiliation: Africa Health Research Institute (AHRI), 4001 Durban, South Africa; Department of Immunology and Microbiology, University of Copenhagen, 1165 Copenhagen, Denmark.
authors.forename: Henrik N
authors.initials: HN
authors.lastname: Kløverpris
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), 138648 Singapore.
authors.forename: Naomi
authors.initials: N
authors.lastname: McGovern
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore (NCCS), 169610 Singapore.
authors.forename: Si-Lin
authors.initials: SL
authors.lastname: Koo
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), 138648 Singapore.
authors.forename: Chiew Yee
authors.initials: CY
authors.lastname: Loh
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), 138648 Singapore.
authors.forename: Shawn
authors.initials: S
authors.lastname: Lim
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, OX1 3SY Oxford, UK.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kurioka
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, OX1 3SY Oxford, UK.
authors.forename: Joannah R
authors.initials: JR
authors.lastname: Fergusson
authors.affiliation: Department of Colorectal surgery, Singapore General Hospital, 169856 Singapore.
authors.forename: Choong-Leong
authors.initials: CL
authors.lastname: Tang
authors.affiliation: Department of Colorectal surgery, Singapore General Hospital, 169856 Singapore.
authors.forename: Ming Hian
authors.initials: MH
authors.lastname: Kam
authors.affiliation: Department of Colorectal surgery, Singapore General Hospital, 169856 Singapore; Colorectal Practice, Mount Elizabeth Medical Centre, 228510 Singapore.
authors.forename: Koh
authors.initials: K
authors.lastname: Dennis
authors.affiliation: Department of Anatomical Pathology, Singapore General Hospital, 169608 Singapore.
authors.forename: Tony Kiat Hon
authors.initials: TKH
authors.lastname: Lim
authors.affiliation: Department of Hepatopancreatobiliary/Transplant Surgery, Singapore General Hospital, 169608 Singapore.
authors.forename: Alexander Chung Yaw
authors.initials: ACY
authors.lastname: Fui
authors.affiliation: Department of Upper GI/Bariatric Surgery, Singapore General Hospital, 169608 Singapore.
authors.forename: Chan Weng
authors.initials: CW
authors.lastname: Hoong
authors.affiliation: KK Women's and Children's Hospital, Department of Reproductive Medicine, 229899 Singapore; Duke-NUS Graduate Medical School, 169857 Singapore.
authors.forename: Jerry Kok Yen
authors.initials: JKY
authors.lastname: Chan
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), 138648 Singapore; New York University School of Medicine, 10012 New york, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Curotto de Lafaille
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Institute of Molecular and Cell Biology (IMCB), 138673 Singapore.
authors.forename: Sriram
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore.
authors.forename: Sonia
authors.initials: S
authors.lastname: Baig
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Shabeer
authors.affiliation: Duke-NUS Graduate Medical School, 169857 Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore; Department of Medicine, National University Health System, 119228 Singapore; Perelman School of Medicine, University of Pennsylvania, 19104 USA.
authors.forename: Sue-Anne Ee Shiow
authors.initials: SES
authors.lastname: Toh
authors.affiliation: KK Women's and Children's Hospital, Department of Otolaryngology, 229899 Singapore.
authors.forename: Henry Kun Kiaang
authors.initials: HKK
authors.lastname: Tan
authors.affiliation: KK Women's and Children's Hospital, Department of Otolaryngology, 229899 Singapore.
authors.forename: Rosslyn
authors.initials: R
authors.lastname: Anicete
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore (NCCS), 169610 Singapore.
authors.forename: Eng-Huat
authors.initials: EH
authors.lastname: Tan
authors.affiliation: Department of Anatomical Pathology, Singapore General Hospital, 169608 Singapore.
authors.forename: Angela
authors.initials: A
authors.lastname: Takano
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, OX1 3SY Oxford, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.affiliation: Africa Health Research Institute (AHRI), 4001 Durban, South Africa.
authors.forename: Alasdair
authors.initials: A
authors.lastname: Leslie
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore (NCCS), 169610 Singapore; Agency for Science, Technology and Research (A(∗)STAR), Genome Institute of Singapore (GIS), 138672 Singapore.
authors.forename: Daniel S W
authors.initials: DSW
authors.lastname: Tan
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore (NCCS), 169610 Singapore; Duke-NUS Graduate Medical School, 169857 Singapore; Agency for Science, Technology and Research (A(∗)STAR), Genome Institute of Singapore (GIS), 138672 Singapore.
authors.forename: Iain Beehuat
authors.initials: IB
authors.lastname: Tan
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), 138648 Singapore.
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.affiliation: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), 138648 Singapore. Electronic address: evan_newell@immunol.a-star.edu.sg.
authors.forename: Evan W
authors.initials: EW
authors.lastname: Newell
mesh_terms: D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007113:Immunity, Innate; D016131:Lymphocyte Subsets / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D010641:Phenotype
keywords: CyTOF; ILC; ILC1; ILC2; ILC3; human; ieILC1