CD5 Surface Expression Marks Intravascular Human Innate Lymphoid Cells That Have a Distinct Ontogeny and Migrate to the Lung
Innate lymphoid cells (ILCs) contribute to immune defense, yet it is poorly understood how ILCs develop and are strategically positioned in the lung. This applies especially to human ILCs due to the difficulty of studying them in vivo. Here we investigated the ontogeny and migration of human ILCs in...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.752104/full |
| _version_ | 1818652361536569344 |
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| author | Arlisa Alisjahbana Yu Gao Natalie Sleiers Elza Evren Demi Brownlie Andreas von Kries Carl Jorns Carl Jorns Nicole Marquardt Jakob Michaëlsson Tim Willinger |
| author_facet | Arlisa Alisjahbana Yu Gao Natalie Sleiers Elza Evren Demi Brownlie Andreas von Kries Carl Jorns Carl Jorns Nicole Marquardt Jakob Michaëlsson Tim Willinger |
| author_sort | Arlisa Alisjahbana |
| collection | DOAJ |
| description | Innate lymphoid cells (ILCs) contribute to immune defense, yet it is poorly understood how ILCs develop and are strategically positioned in the lung. This applies especially to human ILCs due to the difficulty of studying them in vivo. Here we investigated the ontogeny and migration of human ILCs in vivo with a humanized mouse model (“MISTRG”) expressing human cytokines. In addition to known tissue-resident ILC subsets, we discovered CD5-expressing ILCs that predominantly resided within the lung vasculature and in the circulation. CD5+ ILCs contained IFNγ-producing mature ILC1s as well as immature ILCs that produced ILC effector cytokines under polarizing conditions in vitro. CD5+ ILCs had a distinct ontogeny compared to conventional CD5- ILCs because they first appeared in the thymus, spleen and liver rather than in the bone marrow after transplantation of MISTRG mice with human CD34+ hematopoietic stem and progenitor cells. Due to their strategic location, human CD5+ ILCs could serve as blood-borne sentinels, ready to be recruited into the lung to respond to environmental challenges. This work emphasizes the uniqueness of human CD5+ ILCs in terms of their anatomical localization and developmental origin compared to well-studied CD5- ILCs. |
| first_indexed | 2024-12-17T02:20:47Z |
| format | Article |
| id | doaj.art-3581d61e11c14a16a813b6307072b0c7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T02:20:47Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3581d61e11c14a16a813b6307072b0c72022-12-21T22:07:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-11-011210.3389/fimmu.2021.752104752104CD5 Surface Expression Marks Intravascular Human Innate Lymphoid Cells That Have a Distinct Ontogeny and Migrate to the LungArlisa Alisjahbana0Yu Gao1Natalie Sleiers2Elza Evren3Demi Brownlie4Andreas von Kries5Carl Jorns6Carl Jorns7Nicole Marquardt8Jakob Michaëlsson9Tim Willinger10Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenDepartment of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, SwedenDepartment of Transplantation Surgery, Karolinska University Hospital, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenInnate lymphoid cells (ILCs) contribute to immune defense, yet it is poorly understood how ILCs develop and are strategically positioned in the lung. This applies especially to human ILCs due to the difficulty of studying them in vivo. Here we investigated the ontogeny and migration of human ILCs in vivo with a humanized mouse model (“MISTRG”) expressing human cytokines. In addition to known tissue-resident ILC subsets, we discovered CD5-expressing ILCs that predominantly resided within the lung vasculature and in the circulation. CD5+ ILCs contained IFNγ-producing mature ILC1s as well as immature ILCs that produced ILC effector cytokines under polarizing conditions in vitro. CD5+ ILCs had a distinct ontogeny compared to conventional CD5- ILCs because they first appeared in the thymus, spleen and liver rather than in the bone marrow after transplantation of MISTRG mice with human CD34+ hematopoietic stem and progenitor cells. Due to their strategic location, human CD5+ ILCs could serve as blood-borne sentinels, ready to be recruited into the lung to respond to environmental challenges. This work emphasizes the uniqueness of human CD5+ ILCs in terms of their anatomical localization and developmental origin compared to well-studied CD5- ILCs.https://www.frontiersin.org/articles/10.3389/fimmu.2021.752104/fullinnate lymphoid cells (ILC)lungmigrationontogenyhumanized mice |
| spellingShingle | Arlisa Alisjahbana Yu Gao Natalie Sleiers Elza Evren Demi Brownlie Andreas von Kries Carl Jorns Carl Jorns Nicole Marquardt Jakob Michaëlsson Tim Willinger CD5 Surface Expression Marks Intravascular Human Innate Lymphoid Cells That Have a Distinct Ontogeny and Migrate to the Lung Frontiers in Immunology innate lymphoid cells (ILC) lung migration ontogeny humanized mice |
| title | CD5 Surface Expression Marks Intravascular Human Innate Lymphoid Cells That Have a Distinct Ontogeny and Migrate to the Lung |
| title_full | CD5 Surface Expression Marks Intravascular Human Innate Lymphoid Cells That Have a Distinct Ontogeny and Migrate to the Lung |
| title_fullStr | CD5 Surface Expression Marks Intravascular Human Innate Lymphoid Cells That Have a Distinct Ontogeny and Migrate to the Lung |
| title_full_unstemmed | CD5 Surface Expression Marks Intravascular Human Innate Lymphoid Cells That Have a Distinct Ontogeny and Migrate to the Lung |
| title_short | CD5 Surface Expression Marks Intravascular Human Innate Lymphoid Cells That Have a Distinct Ontogeny and Migrate to the Lung |
| title_sort | cd5 surface expression marks intravascular human innate lymphoid cells that have a distinct ontogeny and migrate to the lung |
| topic | innate lymphoid cells (ILC) lung migration ontogeny humanized mice |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.752104/full |
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