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 . Here we investigated the ontogeny and migration of human ILCs with a hu...

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Bibliographic Details
Published in:Frontiers in immunology 2021-11, Vol.12, p.752104-752104
Main Authors: Alisjahbana, Arlisa, Gao, Yu, Sleiers, Natalie, Evren, Elza, Brownlie, Demi, von Kries, Andreas, Jorns, Carl, Marquardt, Nicole, Michaëlsson, Jakob, Willinger, Tim
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Animals
Animals, Genetically Modified
CD5 Antigens - immunology
Cell Differentiation
Cell Movement
Cytokines - immunology
Female
Hematopoietic Stem Cell Transplantation
humanized mice
Humans
Immunity, Innate
Immunology
innate lymphoid cells (ILC)
lung
Lung - immunology
Lymphocytes - immunology
Male
Mice
Middle Aged
migration
ontogeny
Spleen - immunology
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Summary: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 . Here we investigated the ontogeny and migration of human ILCs 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 . 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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.752104