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Development of an Inflammatory CD14(+) Dendritic Cell Subset in Humanized Mice
Humanized mouse models are attractive experimental models for analyzing the development and functions of human dendritic cells (DCs) in vivo. Although various types of DC subsets, including DC type 3 (DC3s), have been identified in humans, it remains unclear whether humanized mice can reproduce hete...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005643/ https://www.ncbi.nlm.nih.gov/pubmed/33790912 http://dx.doi.org/10.3389/fimmu.2021.643040 |
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author | Iwabuchi, Ryutaro Ide, Keigo Terahara, Kazutaka Wagatsuma, Ryota Iwaki, Rieko Matsunaga, Hiroko Tsunetsugu-Yokota, Yasuko Takeyama, Haruko Takahashi, Yoshimasa |
author_facet | Iwabuchi, Ryutaro Ide, Keigo Terahara, Kazutaka Wagatsuma, Ryota Iwaki, Rieko Matsunaga, Hiroko Tsunetsugu-Yokota, Yasuko Takeyama, Haruko Takahashi, Yoshimasa |
author_sort | Iwabuchi, Ryutaro |
collection | PubMed |
description | Humanized mouse models are attractive experimental models for analyzing the development and functions of human dendritic cells (DCs) in vivo. Although various types of DC subsets, including DC type 3 (DC3s), have been identified in humans, it remains unclear whether humanized mice can reproduce heterogeneous DC subsets. CD14, classically known as a monocyte/macrophage marker, is reported as an indicator of DC3s. We previously observed that some CD14(+) myeloid cells expressed CD1c, a pan marker for bona fide conventional DC2 (cDC2s), in humanized mouse models in which human FLT3L and GM-CSF genes were transiently expressed using in vivo transfection (IVT). Here, we aimed to elucidate the identity of CD14(+)CD1c(+) DC-like cells in humanized mouse models. We found that CD14(+)CD1c(+) cells were phenotypically different from cDC2s; CD14(+)CD1c(+) cells expressed CD163 but not CD5, whereas cDC2s expressed CD5 but not CD163. Furthermore, CD14(+)CD1c(+) cells primed and polarized naïve CD4(+) T cells toward IFN-γ(+) Th1 cells more profoundly than cDC2s. Transcriptional analysis revealed that CD14(+)CD1c(+) cells expressed several DC3-specific transcripts, such as CD163, S100A8, and S100A9, and were clearly segregated from cDC2s and monocytes. When lipopolysaccharide was administered to the humanized mice, the frequency of CD14(+)CD1c(+) cells producing IL-6 and TNF-α was elevated, indicating a pro-inflammatory signature. Thus, humanized mice are able to sustain development of functional CD14(+)CD1c(+) DCs, which are equivalent to DC3 subset observed in humans, and they could be useful for analyzing the development and function of DC3s in vivo. |
format | Online Article Text |
id | pubmed-8005643 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80056432021-03-30 Development of an Inflammatory CD14(+) Dendritic Cell Subset in Humanized Mice Iwabuchi, Ryutaro Ide, Keigo Terahara, Kazutaka Wagatsuma, Ryota Iwaki, Rieko Matsunaga, Hiroko Tsunetsugu-Yokota, Yasuko Takeyama, Haruko Takahashi, Yoshimasa Front Immunol Immunology Humanized mouse models are attractive experimental models for analyzing the development and functions of human dendritic cells (DCs) in vivo. Although various types of DC subsets, including DC type 3 (DC3s), have been identified in humans, it remains unclear whether humanized mice can reproduce heterogeneous DC subsets. CD14, classically known as a monocyte/macrophage marker, is reported as an indicator of DC3s. We previously observed that some CD14(+) myeloid cells expressed CD1c, a pan marker for bona fide conventional DC2 (cDC2s), in humanized mouse models in which human FLT3L and GM-CSF genes were transiently expressed using in vivo transfection (IVT). Here, we aimed to elucidate the identity of CD14(+)CD1c(+) DC-like cells in humanized mouse models. We found that CD14(+)CD1c(+) cells were phenotypically different from cDC2s; CD14(+)CD1c(+) cells expressed CD163 but not CD5, whereas cDC2s expressed CD5 but not CD163. Furthermore, CD14(+)CD1c(+) cells primed and polarized naïve CD4(+) T cells toward IFN-γ(+) Th1 cells more profoundly than cDC2s. Transcriptional analysis revealed that CD14(+)CD1c(+) cells expressed several DC3-specific transcripts, such as CD163, S100A8, and S100A9, and were clearly segregated from cDC2s and monocytes. When lipopolysaccharide was administered to the humanized mice, the frequency of CD14(+)CD1c(+) cells producing IL-6 and TNF-α was elevated, indicating a pro-inflammatory signature. Thus, humanized mice are able to sustain development of functional CD14(+)CD1c(+) DCs, which are equivalent to DC3 subset observed in humans, and they could be useful for analyzing the development and function of DC3s in vivo. Frontiers Media S.A. 2021-03-15 /pmc/articles/PMC8005643/ /pubmed/33790912 http://dx.doi.org/10.3389/fimmu.2021.643040 Text en Copyright © 2021 Iwabuchi, Ide, Terahara, Wagatsuma, Iwaki, Matsunaga, Tsunetsugu-Yokota, Takeyama and Takahashi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Iwabuchi, Ryutaro Ide, Keigo Terahara, Kazutaka Wagatsuma, Ryota Iwaki, Rieko Matsunaga, Hiroko Tsunetsugu-Yokota, Yasuko Takeyama, Haruko Takahashi, Yoshimasa Development of an Inflammatory CD14(+) Dendritic Cell Subset in Humanized Mice |
title | Development of an Inflammatory CD14(+) Dendritic Cell Subset in Humanized Mice |
title_full | Development of an Inflammatory CD14(+) Dendritic Cell Subset in Humanized Mice |
title_fullStr | Development of an Inflammatory CD14(+) Dendritic Cell Subset in Humanized Mice |
title_full_unstemmed | Development of an Inflammatory CD14(+) Dendritic Cell Subset in Humanized Mice |
title_short | Development of an Inflammatory CD14(+) Dendritic Cell Subset in Humanized Mice |
title_sort | development of an inflammatory cd14(+) dendritic cell subset in humanized mice |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005643/ https://www.ncbi.nlm.nih.gov/pubmed/33790912 http://dx.doi.org/10.3389/fimmu.2021.643040 |
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