Google Scholar, Mirza R, Dipietro LA, Koh TJ (2009) Selective and specific macrophage ablation is detrimental to wound healing in mice. Methods 432, 35–49 (2016). Interestingly, evidence supporting an HSC origin of LCs in mice can be found in reports supporting an EMP origin of LCs. doi:10.1038/jid.2009.429, 32. Nature 454:428–435.
Keywords: Langerhans cells, inflammatory dendritic epidermal cells, skin inflammation, resident macrophages, dendritic cells Citation: Otsuka M, Egawa G and Kabashima K (2018) Uncovering the Mysteries of Langerhans Cells, Inflammatory Dendritic Epidermal Cells, and Monocyte-Derived Langerhans Cell-Like Cells in the Epidermis.
doi:10.1046/j.1523-1747.2000.00912.x, Tauber AI (2003) Metchnikoff and the phagocytosis theory.
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For instance, a substantial number (30%) of LCs were recorded in 1-year-old Flt3CreRosa26YFP reporter mice (Gomez Perdiguero et al., 2015), in which HSCs and HSCs-derived hematopoietic progenitors were labeled upon Cre-mediated excision (Christensen and Weissman, 2001; Gomez Perdiguero et al., 2015). J. 125, 1154–1156 (2010). The origin of Langerhans cells (LCs), which are skin epidermis-resident macrophages, remains unclear. 38, 3050–3059 (2008). Immunity 12, 71–81 (2000). Kaplan DH, Li MO, Jenison MC, Shlomchik WD, Flavell RA, Shlomchik MJ. Article doi:10.1016/S0301-472X(01)00669-5, 11. Indian J Endocrinol Metab 15(Suppl 4):S281–S288. Immunity 37, 60–73 (2012). http://dx.doi.org/10.1016/j.jaci.2016.12.970 (2017). Immunol.
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To test this hypothesis, we artificially divided the VDA region into four positions, namely position 1 (P1) to position 4 (P4), from the anterior to posterior (Figure 3F) and heat-shocked only one position in each Tg(mpeg1:loxP-DsRedx-loxP-GFP);Tg(hsp70:mCherry-T2a-CreERT2) embryo. doi:10.1111/1523-1747.ep12343596, 48. In the revised manuscript, we have included the marrow transplant analysis, which we performed previously, showing that the transplanted adult kidney marrow cells are indeed capable of giving rise to adult LCs in the recipients (subsection “Adult tissue-resident macrophages are largely associated with HSCs during transplantation”). Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia. Runx3 regulates mouse TGF-β-mediated dendritic cell function and its absence results in airway inflammation. doi:10.1016/j.immuni.2012.11.001, 23. Nat Immunol 18, 1068–1075 (2017). Eventually, most adult LCs were derived from the VDA region in the zebrafish. Ouchi T, Kubo A, Yokouchi M, Adachi T, Kobayashi T, Kitashima DY, et al. (D) Anti-GFP staining indicates that GFP+ LCs are mainly detected in the VDA-labelled fish, but not the RBI- and PBI-labelled fish in adulthood. & Mortha, A. Eur. 182, 921–933 (2009).
The authors should consider marrow transplants to test whether adult HSCs can give rise to these cells.
& Nussenzweig, M.C. However, this will require a HSC-specific promoter, which is currently not available in zebrafish. These studies suggested that, perhaps similar to zebrafish, this non-HSC population of cells also exists in the mammalian aorta endothelium.
To strengthen the relationship between HSCs and LCs the authors should pursue experiments to show multilineage contribution and LC development from single cells. 17, 451–460 (2017). Med.
Acute ablation of Langerhans cells enhances skin immune responses. n = 5, 5, 5 and 6 for the RBI-, VDA-, PBI-, and non-heat-shocked control fish analyzed at adulthood, respectively. Immunol. Antonopoulos, C. et al. Batf3 deficiency reveals a critical role for CD8α+ dendritic cells in cytotoxic T cell immunity.
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