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      Langerin-expressing dendritic cells in human tissues are related to CD1c + dendritic cells and distinct from Langerhans cells and CD141 high XCR1 + dendritic cells

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          Abstract

          Langerin is not restricted to Langerhans cells, but expressed at low levels by CD1c + dendritic cells and is inducible by TGFβ in humans.

          Abstract

          Langerin is a C-type lectin expressed at high level by LCs of the epidermis. Langerin is also expressed by CD8 +/CD103 + XCR1 + cross-presenting DCs of mice but is not found on the homologous human CD141 high XCR1 + myeloid DC. Here, we show that langerin is expressed at a low level on DCs isolated from dermis, lung, liver, and lymphoid tissue and that langerin + DCs are closely related to CD1c + myeloid DCs. They are distinguishable from LCs by the level of expression of CD1a, EpCAM, CD11b, CD11c, CD13, and CD33 and are found in tissues and tissue-draining LNs devoid of LCs. They are unrelated to CD141 high XCR1 + myeloid DCs, lacking the characteristic expression profile of cross-presenting DCs, conserved between mammalian species. Stem cell transplantation and DC deficiency models confirm that dermal langerin + DCs have an independent homeostasis to LCs. Langerin is not expressed by freshly isolated CD1c + blood DCs but is rapidly induced on CD1c + DCs by serum or TGF- β via an ALK-3-dependent pathway. These results show that langerin is expressed outside of the LC compartment of humans and highlight a species difference: langerin is expressed by the XCR1 + "DC1" population of mice but is restricted to the CD1c + "DC2" population of humans (homologous to CD11b + DCs in the mouse).

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          Most cited references33

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          The origin and development of nonlymphoid tissue CD103+ DCs

          CD103+ dendritic cells (DCs) in nonlymphoid tissues are specialized in the cross-presentation of cell-associated antigens. However, little is known about the mechanisms that regulate the development of these cells. We show that two populations of CD11c+MHCII+ cells separated on the basis of CD103 and CD11b expression coexist in most nonlymphoid tissues with the exception of the lamina propria. CD103+ DCs are related to lymphoid organ CD8+ DCs in that they are derived exclusively from pre-DCs under the control of fms-like tyrosine kinase 3 (Flt3) ligand, inhibitor of DNA protein 2 (Id2), and IFN regulatory protein 8 (IRF8). In contrast, lamina propria CD103+ DCs express CD11b and develop independently of Id2 and IRF8. The other population of CD11c+MHCII+ cells in tissues, which is CD103−CD11b+, is heterogenous and depends on both Flt3 and MCSF-R. Our results reveal that nonlymphoid tissue CD103+ DCs and lymphoid organ CD8+ DCs derive from the same precursor and follow a related differentiation program.
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            Characterization of human blood dendritic cell subsets.

            Dendritic cells (DCs) are key antigen-presenting cells for stimulating immune responses and they are now being investigated in clinical settings. Although defined as lineage-negative (Lin(-)) HLA-DR(+) cells, significant heterogeneity in these preparations is apparent, particularly in regard to the inclusion or exclusion of CD14(+), CD16(+), and CD2(+) cells. This study used flow cytometry and a panel of monoclonal antibodies (mAbs), including reagents from the 7th Leukocyte Differentiation Antigen Workshop, to define the cellular composition of 2 standardized peripheral blood mononuclear cell (PBMCs)-derived Lin(-) HLA-DR(+) preparations. Lin(-) cells were prepared from PBMCs by depletion with CD3, CD14, CD19, CD11b, and either CD16 or CD56 mAbs. Analysis of the CD16-replete preparations divided the Lin(-) HLA-DR(+) population into 5 nonoverlapping subsets (mean +/- 1 SD): CD123 (mean = 18.3% +/- 9.7%), CD1b/c (18.6% +/- 7.6%), CD16 (49.6% +/- 8.5%), BDCA-3 (2.7% +/- 1.4%), and CD34 (5.0% +/- 2.4%). The 5 subsets had distinct phenotypes when compared with each other, monocytes, and monocyte-derived DCs (MoDCs). The CD85 family, C-type lectins, costimulatory molecules, and differentiation/activation molecules were also expressed differentially on the 5 Lin(-) HLA-DR(+) subsets, monocytes, and MoDCs. The poor viability of CD123(+) DCs in vitro was confirmed, but the CD16(+) CD11c(+) DC subset also survived poorly. Finally, the individual subsets used as stimulators in allogeneic mixed leukocyte reactions were ranked by their allostimulatory capacity as CD1b/c > CD16 > BDCA-3 > CD123 > CD34. These data provide an opportunity to standardize the DC populations used for future molecular, functional and possibly even therapeutic studies.
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              Human dendritic cell subsets

              Dendritic cells are highly adapted to their role of presenting antigen and directing immune responses. Developmental studies indicate that DCs originate independently from monocytes and tissue macrophages. Emerging evidence also suggests that distinct subsets of DCs have intrinsic differences that lead to functional specialisation in the generation of immunity. Comparative studies are now allowing many of these properties to be more fully understood in the context of human immunology.
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                Author and article information

                Journal
                J Leukoc Biol
                J. Leukoc. Biol
                jleub
                jleub
                JLB
                Journal of Leukocyte Biology
                Society for Leukocyte Biology (Bethesda, MD, USA )
                0741-5400
                1938-3673
                April 2015
                16 December 2014
                16 December 2014
                : 97
                : 4
                : 627-634
                Affiliations
                [1]Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom
                Author notes
                [1]

                Current affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.

                [2 ]Correspondence: Institute of Cellular Medicine, Newcastle University, Framlington Pl., Newcastle upon Tyne, NE2 4HH, United Kingdom. E-mail: matthew.collin@ 123456ncl.ac.uk ; Twitter: http://www.twitter.com/HumanDCLab
                Article
                JLB_1HI0714-351R
                10.1189/jlb.1HI0714-351R
                4370053
                25516751
                705485ce-4ad1-4db3-a856-087a280249d0
                © The Author(s)

                This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) ( http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 July 2014
                : 01 October 2014
                : 16 October 2014
                Page count
                Pages: 8
                Categories
                Spotlight on Leading Edge Research
                Custom metadata
                v1

                Hematology
                antigen presenting cell,differentiation,hsct,dcml deficiency,gata2
                Hematology
                antigen presenting cell, differentiation, hsct, dcml deficiency, gata2

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