Human dendritic cell differentiation in hematopoietic stem cell-transplanted NOG hFLT3L Tg/mFlt3 KO humanized mice.

Autor: Mu Y; Central Institute for Experimental Medicine and Life Science, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan; Department of Immunology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, 55901, USA., Ohno Y; Central Institute for Experimental Medicine and Life Science, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan., Mochizuki M; Central Institute for Experimental Medicine and Life Science, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan., Kawai K; Central Institute for Experimental Medicine and Life Science, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan., Goto M; Central Institute for Experimental Medicine and Life Science, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan., Ogura T; Central Institute for Experimental Medicine and Life Science, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan., Takahashi R; Central Institute for Experimental Medicine and Life Science, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan., Ito M; Central Institute for Experimental Medicine and Life Science, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan., Ito R; Central Institute for Experimental Medicine and Life Science, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan. Electronic address: rito@ciea.or.jp.
Jazyk: angličtina
Zdroj: Immunology letters [Immunol Lett] 2024 Dec; Vol. 270, pp. 106943. Date of Electronic Publication: 2024 Nov 12.
DOI: 10.1016/j.imlet.2024.106943
Abstrakt: Human immune system-reconstituted humanized mice are useful animal models to study human immunology in vivo. Human hematopoietic stem cell-transferred NOG mice are well recognized as humanized immune system models with reconstitution of mature lymphoid lineage cells such as T and B cells. However, human myeloid lineage cells including dendritic cells (DCs) do not fully differentiate in conventional NOG mice. DCs play a crucial role in adaptive immunity through antigen presentation to T cells to acquire antigen specificity. In this study, we established a novel humanized mouse with human DC differentiation. To induce DCs, we generated human Fms-like tyrosine kinase 3 ligand (hFLT3L) transgenic NOG (hFLT3L-Tg) mice and transferred human CD34 + hematopoietic stem cells (HSC) into them. Unexpectedly, low frequency of human cell engraftment was observed in the hFLT3L-Tg mice after HPC reconstitution. In the Tg mice, mouse CD11b + Gr1 - myeloid cells were markedly expanded in the bone marrow due to the cross-reaction between hFLT3L and mouse Flt3 receptor, and these myeloid leukemia-like cells interfered with the engraftment of human hematopoietic cells in hFLT3L-Tg mice. To avoid this cross-reaction, we further generated NOG FLT3 receptor KO (mFlt3 KO) mice by CRISPR/Cas9 technique, and the KO mice combined with hFLT3L Tg mice to create hFLT3L Tg/mFlt3 KO (FL Tg/KO) mice. Mouse CD11b + Gr1 - leukemia-like cells did not proliferate in FL Tg/KO mice due to blockade of the FLT3 signals in mouse leukocytes. After human HSC transplantation, human CD45 + cells were successfully engrafted in FL Tg/KO mice. Furthermore, major subsets of human DC populations, cDC1, cDC2, and pDC, and skin Langerhans cells were significantly differentiated in FL Tg/KO mice. Therefore, these humanized mouse models are potentially valuable in the investigation of DC-mediated human adaptive immune responses in vivo.
Competing Interests: Declaration of competing interest No financial interest/relationships relating to the topic of this article have been declared.
(Copyright © 2024 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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