Langerin-expressing dendritic cells in human tissues are related to CD1c+ dendritic cells and distinct from Langerhans cells and CD141high XCR1+ dendritic cells

Bigley, Venetia; McGovern, Naomi; Milne, Paul; Dickinson, Rachel; Pagan, Sarah; Cookson, Sharon; Haniffa, Muzlifah; Collin, Matthew

doi:10.1189/jlb.1hi0714-351r

Cited by 106 publications

(131 citation statements)

References 41 publications

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“…The critical role of notch signaling in permitting LC development from monocytes was first reported in response to DLL1. 22 16 and rapidly acquire LC-like properties when exposed to GM-CSF and TGF-b. 17,18 In vitro differentiation experiments presented here clearly show that 2 pathways may generate langerin high cells and that DLL4 provides a more potent signal for monocytes than DLL1.…”

Section: V600ementioning

confidence: 99%

“…5 These studies support a model in which MS-LCH arises in the hematopoietic stem cells (HSCs) and is disseminated to the periphery by myeloid cells carrying somatic mutation. 13 16 and readily acquire a Langerhans cell-like phenotype in vitro. 17,18 The differentiation potentials of monocytes and blood DCs overlap, and monocyte-derived DCs bear many markers in common with CD1c 1 myeloid DCs.…”

Section: Introductionmentioning

confidence: 99%

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Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults

Milne

Bigley

Bacon

et al. 2017

Blood

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145

134

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Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are rare histiocytic disorders induced by somatic mutation of MAPK pathway genes. BRAF V600E mutation is the most common mutation in both conditions and also occurs in the hematopoietic neoplasm hairy cell leukemia (HCL). It is not known if adult LCH or ECD arises from hematopoietic stem cells (HSCs), nor which potential blood borne precursors lead to the formation of histiocytic lesions. In this study, BRAF V600E allele-specific polymerase chain reaction was used to map the neoplastic clone in 20 adults with LCH, ECD, and HCL. BRAF V600E was tracked to classical monocytes, nonclassical monocytes, and CD1c 1 myeloid dendritic cells (DCs) in the blood, and mutations were observed in HSCs and myeloid progenitors in the bone marrow of 4 patients. The pattern of involvement of peripheral blood myeloid cells was indistinguishable between LCH and ECD, although the histiocytic disorders were distinct to HCL. As reported in children, detection of BRAF V600E in peripheral blood of adults was a marker of active multisystem LCH. The healthy counterparts of myeloid cells affected by BRAF mutation had a range of differentiation potentials depending on exogenous signals. CD1c 1 DCs acquired high langerin and CD1a with granulocyte-macrophage colony-stimulating factor and transforming growth factor b alone, whereas CD14 1 classical monocytes required additional notch ligation. Both classical and nonclassical monocytes, but not CD1c 1 DCs, made foamy macrophages easily in vitro with macrophage colony-stimulating factor and human serum. These studies are consistent with a hematopoietic origin and >1 immediate cellular precursor in both LCH and ECD. (Blood. 2017;130(2):167-175)

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Section: V600ementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults

Milne

Bigley

Bacon

et al. 2017

Blood

Self Cite

145

134

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“…11,12 However, the existence of an equivalent of this langerin 1 dDC subpopulation in human skin has been questioned, 13 although very recently, a langerin 1 APC subpopulation has also been detected in the human dermis. 14 Because of their APC-restricted expression pattern and their function as antigen-uptake receptors for processing and presentation, CLRs have often been studied as targeting receptors for vaccination. 15,16 Antigen targeting to DEC-205, DCIR, CLEC9a, dectin-1, and DC-SIGN on DCs results in receptor internalization and enhanced antigen-specific CD4 1 and CD8 1 T-cell responses.…”

Section: Introductionmentioning

confidence: 99%

Langerin-mediated internalization of a modified peptide routes antigens to early endosomes and enhances cross-presentation by human Langerhans cells

et al. 2015

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The potential of the skin immune system to generate immune responses is well established, and the skin is actively exploited as a vaccination site. Human skin contains several antigen-presenting cell subsets with specialized functions. In particular, the capacity to cross-present exogenous antigens to CD8+ T cells is of interest for the design of effective immunotherapies against viruses or cancer. Here, we show that primary human Langerhans cells (LCs) were able to cross-present a synthetic long peptide (SLP) to CD8 T cells. In addition, modification of this SLP using antibodies against the receptor langerin, but not dectin-1, further enhanced the cross-presenting capacity of LCs through routing of internalized antigens to less proteolytic early endosome antigen 1 early endosomes. The potency of LCs to enhance CD8 T-cell responses could be further increased through activation of LCs with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid (pI:C). Altogether, the data provide evidence that human LCs are able to cross-present antigens after langerin-mediated internalization. Furthermore, the potential for antigen modification to target LCs specifically provides a rationale for generating effective anti-tumor or anti-viral cytotoxic T lymphocyte responses.

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“…In the dermis, CD1c + DCs co-express CD1a, while intestinal CD1c + DCs express CD103 (Watchmaker et al, 2014). It is worth mentioning that dermal CD1a + DCs can be further subdivided into two subsets based on the expression of Langerin (Bigley et al, 2015). Blood CD1c + DCs are closely related to Langerin + dermal DCs that express CD1a, CD11b, CD11c as well as a lower level of Langerin expression (Bigley et al, 2015).…”

Section: 34) Human Cd1c + Dcsmentioning

confidence: 99%

“…It is worth mentioning that dermal CD1a + DCs can be further subdivided into two subsets based on the expression of Langerin (Bigley et al, 2015). Blood CD1c + DCs are closely related to Langerin + dermal DCs that express CD1a, CD11b, CD11c as well as a lower level of Langerin expression (Bigley et al, 2015). Similarly, McGovern et al previously reported that CD1c + DCs with a lower CD14 expression are localised within the human dermal tissue (McGovern et al, 2014).…”

Section: 34) Human Cd1c + Dcsmentioning

confidence: 99%

The role of human CD1c+ DCs at activating innate and adaptive immune responses

Mok¹

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In humans, several dendritic cell (DC) subsets have been identified, including the CD1c + DCs, CD141 + DCs and plasmacytoid DC (pDC). It has been suggested that human CD141 + DCs play a role in cross-presentation leading to the induction of cytotoxic T lymphocyte (CTL) responses that are important for immunity against tumours and intracellular pathogens. pDCs are known to be major responders against viruses through secretion of Type I interferons (IFNs).

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Langerin-expressing dendritic cells in human tissues are related to CD1c+ dendritic cells and distinct from Langerhans cells and CD141high XCR1+ dendritic cells

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

Cited by 106 publications

References 41 publications

Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults

Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults

Langerin-mediated internalization of a modified peptide routes antigens to early endosomes and enhances cross-presentation by human Langerhans cells

The role of human CD1c+ DCs at activating innate and adaptive immune responses

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