Björn E Clausen

• Ph.D.
• Professor at Universitätsmedizin der Johannes Gutenberg-Universität Mainz

In this issue of JEM, Lim et al. (https://doi.org/10.1084/jem.20191810) provide exciting new evidence that talin1 plays an essential role in dendritic cell (DC) maturation and activation. Using conditional knockout mice, they demonstrate that talin1 promotes the formation of a preassembled TLR-Myddosome signaling complex in steady-state DCs but not...

The cell adhesion molecule E-cadherin is a major component of adherens junctions and marks Langerhans cells (LC), the only dendritic cell (DC) population of the epidermis. LC form a dense network and attach themselves to the surrounding keratinocytes via homophilic E-cadherin binding. LC activation, mobilization, and migration require a reduction i...

Dendritic cells (DC) fulfill an essential sentinel function within the immune system, acting at the interface of innate and adaptive immunity. The DC family, both in mouse and man, shows high functional heterogeneity in order to orchestrate immune responses toward the immense variety of pathogens and other immunological threats. In this review, we...

Dendritic cells (DC) are a heterogeneous family of professional antigen-presenting cells classically recognized as most potent inducers of adaptive immune responses. In this respect, Langerhans cells have long been considered to be prototypic immunogenic DC in the skin. More recently this view has considerably changed. The generation of in vivo cel...

Background and objective Asthma is a chronic inflammatory disease characterized by dysregulated cytokine expression. The RNA-binding protein KSRP reduces the expression of several pro-inflammatory mediators. Therefore, we investigated whether KSRP modulates Th2-associated immune responses in vivo in an ovalbumin-induced (OVA) allergic asthma model...

Conventional dendritic cells (cDCs) are potent antigen-presenting cells (APCs) that integrate signals from their environment allowing them to direct situation-adapted immunity. Thereby they harbor great potential for being targeted in vaccination, autoimmunity, and cancer. Here, we use fate mapping, functional analyses, and comparative cross-specie...

Dendritic cells (DCs) are present in almost all tissues, where they act as sentinels involved in innate recognition and the initiation of adaptive immune responses. The DC family consists of several cell lineages that are heterogenous in their development, phenotype, and function. Within these DC lineages, further subdivisions exist, resulting in s...

Current evidence suggests that ontogeny may account for the functional heterogeneity of some tissue macrophages, but not others. Here, we asked whether developmental origin drives different functions of skin Langerhans cells (LCs), an embryo-derived mononuclear phagocyte with features of both tissue macrophages and dendritic cells. Using time-cours...

Macroautophagy (often-named autophagy), a catabolic process involving autophagy-related (Atg) genes, prevents the accumulation of harmful cytoplasmic components and mobilizes energy reserves in long-lived and self-renewing cells. Autophagy deficiency affects antigen presentation in conventional dendritic cells (DCs) without impacting their survival...

Due to its capacity to drive osteoclast differentiation, the receptor activator of nuclear factor kappa-β ligand (RANKL) is believed to exert a pathological influence in periodontitis. However, RANKL was initially identified as an activator of dendritic cells (DCs), expressed by T cells, and exhibits diverse effects on the immune system. Hence, it...

GSK-3β plays a critical role in regulating the Wnt/β-catenin signaling pathway, and manipulating GSK-3β in dendritic cells (DCs) has been shown to improve the antitumor efficacy of DC vaccines. Since the inhibition of GSK-3β leads to the activation of β-catenin, we hypothesize that blocking GSK-3β in DCs negatively regulates DC-mediated CD8 T cell...

Recent studies have demonstrated that β-catenin in dendritic cells (DCs) serves as a key mediator in promoting both CD4 and CD8 T cell tolerance, although the mechanisms underlying how β-catenin exerts its functions remain incompletely understood. Here, we report that activation of β-catenin leads to the up-regulation of inhibitory molecule T-cell...

Colorectal cancer (CRC) is a complex and heterogeneous disease characterized by dysregulated interactions between tumor cells and the immune system. The tumor microenvironment plays a pivotal role in cancer initiation as well as progression, with myeloid immune cells such as dendritic cell and macrophage subsets playing diverse roles in cancer immu...

Tissue-resident memory CD8+ T cells (TRM) reside at sites of previous infection, providing protection against reinfection with the same pathogen. In the skin, TRM patrol the epidermis, where keratinocytes are the entry site for many viral infections. Epidermal TRM react rapidly to cognate antigen encounter with the secretion of cytokines and differ...

The skin and the oral mucosa represent interfaces to the environment that are constantly exposed to pathogens and harmless foreign antigens such as commensal bacteria. Both barrier organs share the presence of Langerhans cells (LC), distinctive members of the heterogeneous family of antigen-presenting dendritic cells (DC) that have the unique abili...

The main cause of malignancy-related mortality is metastasis. Although metastatic progression is driven by diverse tumor-intrinsic mechanisms, there is a growing appreciation for the contribution of tumor-extrinsic elements of the tumor microenvironment, especially macrophages, which correlate with poor clinical outcomes. Macrophages consist of bon...

Psoriasis is an IL-23/IL-17-mediated inflammatory autoimmune dermatosis and ultraviolet B (UVB) may contribute to immunosuppression and ameliorate associated symptoms. One of the pathophysiology underlying UVB therapy is through the production of cis-urocanic acid (cis-UCA) from keratinocytes. However, the detailed mechanism is yet to be fully unde...

To specifically tailor immune responses to a given pathogenic threat, dendritic cells (DC) are highly heterogeneous and comprise many specialized subtypes, including conventional DC (cDC) and monocyte‐derived DC (MoDC), each with distinct developmental and functional characteristics. However, the functional relationship between cDC and MoDC is not...

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state‐of‐the‐art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human DC from lymphoid organs, and various non‐lymphoid tissues. Within this chap...

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state‐of‐the‐art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various non‐lymphoid tissues....

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state‐of‐the‐art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various nonlymphoid tissues. D...

Macroautophagy (often-named autophagy), a catabolic process requiring activity of autophagy-related (Atg) genes, prevents accumulation of harmful cytoplasmic components and mobilizes energy reserves in long-lived and self-renewing cells. Autophagy deficiency affects antigen presentation in conventional dendritic cells (DCs) without impacting their...

Heterodimeric ß2 integrin surface receptors (CD11a-d/CD18) are specifically expressed by leukocytes that contribute to pathogen uptake, cell migration, immunological synapse formation and cell signaling. In humans, the loss of CD18 expression results in leukocyte adhesion deficiency syndrome (LAD-)1, largely characterized by recurrent severe infect...

Significance Conventional dendritic cells (cDC) and macrophages display a high phenotypic and functional heterogeneity. ADAM10 regulates diverse cellular activities via so-called ectodomain shedding of cell-surface proteins. Here, we report that mice with a CD11c-specific deletion of ADAM10 exhibit defective cDC subset homeostasis in the splenic ma...

Innate-like T cells, including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells and γδ T cells, are present in various barrier tissues, including the lung. They carry out protective responses during infections, but the mechanisms for protection are not completely understood. Here, we investigated their roles duri...

Sodium can accumulate in the skin, at concentrations exceeding serum levels. High sodium environment can lead to pathogenic T helper (Th)17 cell expansion. Psoriasis is a chronic inflammatory skin disease in which interleukin (IL)-17-producing Th17 cells play a crucial role. In an observational study, we measured skin sodium content in psoriasis pa...

The original concept stated that immature dendritic cells (DC) act tolerogenically whereas mature DC behave strictly immunogenically. Meanwhile, it is also accepted that phenotypically mature stages of all conventional DC subsets can promote tolerance as steady-state migratory DC by transporting self-antigens to lymph nodes to exert unique function...

Acute graft-versus-host disease (aGVHD) induced by allogenic hematopoietic stem cell transplantation is an immunological disorder in which donor lymphocytes attack recipient organs. It has been proven that recipient nonhematopoietic tissue cells, like keratinocytes, are sufficient as immunological targets for allogenic donor T cells, while Langerha...

Background Conventional type 1 dendritic cells (cDC1s) control anti‐viral and anti‐tumor immunity by inducing antigen‐specific cytotoxic CD8⁺ T‐cell responses. Controversy exists whether cDC1s also control CD4⁺ T helper 2 (Th2) cell responses, since suppressive and activating roles have been reported. DC activation status, controlled by the transcr...

Kupffer cells (KCs) are liver-resident macrophages that self-renew by proliferation in the adult independently from monocytes. However, how they are maintained during non-alcoholic steatohepatitis (NASH) remains ill defined. We found that a fraction of KCs derived from Ly-6C⁺ monocytes during NASH, underlying impaired KC self-renewal. Monocyte-deri...

Significance AhR, which is expressed in many epithelial, mucosal, and immune cells, represents a vital cellular sensor of environmental factors. Immune regulation by AhR can be cell, tissue, and ligand specific. Langerhans cells (LC), professional antigen presenting cells in the epidermis, govern the immunological barrier against environmental thre...

16th International Workshop on Langerhans Cells (LC2019)

Vesicular stomatitis virus (VSV) is an insect-transmitted rhabdovirus that is neurovirulent in mice. Upon peripheral VSV infection, CD169⁺ subcapsular sinus (SCS) macrophages capture VSV in the lymph, support viral replication, and prevent CNS neuroinvasion. To date, the precise mechanisms controlling VSV infection in SCS macrophages remain incompl...

One major characteristic of skin-related cancers is the loss of skin-resident dendritic cell populations. In the tg(Grm1)EPv mouse model, ectopic expression of the metabotropic glutamate receptor-1 in melanocytes leads to a highly proliferative and antiapoptotic phenotype, resulting in melanoma formation within the dermis. The slow progression of t...

Breach of tolerance to gluten leads to the chronic small intestinal enteropathy celiac disease. A key event in celiac disease development is gluten-dependent infiltration of activated cytotoxic intraepithelial lymphocytes (IELs), which cytolyze epithelial cells causing crypt hyperplasia and villous atrophy. The mechanisms leading to gluten-dependen...

Dendritic cells (DCs) are important inducers and regulators of T-cell responses. They are able to activate and modulate the differentiation of CD4⁺ and CD8⁺ T cells. In the skin, there are at least five phenotypically distinct DC subpopulations that can be distinguished by differential expression of the cell surface markers CD207, CD103, and CD11b....

Besides skin inflammation, patients with severe psoriasis suffer from an increased risk of cardiovascular mortality. IL-17A plays a central role in the development of psoriasis and might connect skin and vascular disease. The aim of this study was to clarify whether anti-IL-17A therapy could also ameliorate the vascular dysfunction associated with...

Dendritic cells (DCs) express the ecto-5′-nucleotidase CD73 that generates immunosuppressive adenosine (Ado) by dephosphorylation of extracellular Ado monophosphate and diphosphate. To investigate whether CD73-derived Ado has immune-suppressive activity, 2,4-dinitrothiocyanobenzene (DNTB) was applied to skin of wild-type (WT) or CD73-deficient (CD7...

15th International Symposium on Dendritic Cells (DC2018)

The opportunistic fungal pathogen Candida albicans frequently causes diseases such as oropharyngeal candidiasis (OPC) in immunocompromised individuals. Although it is well appreciated that the cytokine IL-17 is crucial for protective immunity against OPC, the cellular source and the regulation of this cytokine during infection are still a matter of...

Dynamic changes in the MHCII+ MNP network upon OPC. WT mice were infected with yCherry-expressing C. albicans strain CAF-yCherry. Microscopy analysis of C. albicans (red) and MHCII+ MNPs (green) in epithelial sheets obtained from naïve and infected WT mice. Representative pictures from one out of two independent experiments are shown (scale bar = 1...

Flow cytometric analysis of IL-1β and IL-6 expression in CD11c+MHCII+ MNP subsets in the tongue during acute OPC. (A) Gating strategy for identifying pro-IL-1β-expressing cells in CD11c+MHCII+ MNP subsets in the tongue of infected WT mice. Cells were gated on viable CD45+ cells. Numbers indicate the % of cells in the gate. The same gating strategy...

Identification of IL-17A-producing lymphocytes in the murine tongue by intracellular staining and flow cytometry. (A) Gating strategy for identifying CD90+IL-17A+ cell populations in the tongue of infected mice. (B) Analysis of CD90+IL-17A+ cells in the tongue of infected WT and Il17af-/- animals. (C) Analysis of IL-17A and IL-17F co-expression by...

Phenotype of IL-17A-producing cells during acute OPC. (A) Flow cytometric analysis of the TCRβ+, TCRγδ+ and TCR- subsets for the indicated markers. Pre-gating is on CD45+CD90+ (upper panels) or CD45+CD90+IL-17A+ cells (lower panels). Representative plots from one out of two or three independent experiments are shown. Numbers indicate the % of cells...

IL-1 and IL-6 play a redundant role for IL-17 production. IL-17A+ cellular subsets in the tongue of infected WT and Il1ra-/- animals (A-B) or IL-17A+ cellular subsets in the tongue of infected WT mice that were treated with anti-IL-6 antibody or left untreated (C-D). (A, C) Representative plots. Pre-gating is on CD45+CD90+ cells. Numbers indicate t...

Quantification of IL-1β and IL-6 transcripts in sorted tongue cell populations. (A, B) RT qPCR analysis of Il23a (A), Il1b (B, left) and Il6 (B, right) expression in sorted CD11c+MHCII+EpCam+ MNPs, CD11c+MHCII+EpCam- MNPs, neutrophils and epithelial cells from infected WT (B) or Il23a-/- mice (A). Each symbol represents one animal, the mean of each...

Effect of neutrophils and monocyte deficiency on IL-17 production. (A) Gating strategy for identifying myeloid cell populations in the tongue of infected mice, including CD90-CD11c+MHCII+ MNPs, CD11c-MHCII-CD11b+Ly6G+ neutrophils and CD11c-MHCII-CD11b+Ly6Chigh monocytes. Numbers indicate the % of cells in the gate. Numbers in the histograms in A in...

Characterization of tongue-resident MNP subsets in naïve animals. (A) Experimental scheme for bone marrow chimera to investigate radio-resistance of tongue-resident CD11c+MHCII+ MNPs. (B) Flow cytometric analysis of tongue-resident CD11c+MHCII+ MNP subsets for the expression of CD45.1 and CD45.2 in naïve, reconstituted WT animals. Representative pl...

Hematopoietic and non-hematopoietic cells provide IL-1β and IL-6 during acute OPC. (A) Expression of pro-IL-1β and IL-6 was analyzed by flow cytometry in CD11c+MHCII+ (P1) and CD11c-MHCII- populations (P2) in the tongue of naïve and infected WT mice. Pre-gating is on CD45+ cells. (B) Flow cytometric analysis of CD45- tongue cells from naïve and inf...

Mucosal Langerhans cells (LCs) originate from pre–dendritic cells and monocytes. However, the mechanisms involved in their in situ development remain unclear. Here, we demonstrate that the differentiation of murine mucosal LCs is a two-step process. In the lamina propria, signaling via BMP7-ALK3 promotes translocation of LC precursors to the epithe...

Functional predictions for transcriptional changes in rIL-2-treated LCs via Ingenuity Pathway Analysis.

Co-localization of langerin and Dsg3 signals in epidermal LCs.

Langerhans cells (LCs) are antigen-presenting cells in the epidermis whose roles in antigen-specific immune regulation remain incompletely understood. Desmoglein 3 (Dsg3) is a keratinocyte cell-cell adhesion molecule critical for epidermal integrity and an autoantigen in the autoimmune blistering disease pemphigus. Although antibody-mediated diseas...

CD103⁺CD11b⁺ dendritic cells (DCs) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGFβR1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1 results in markedly fewer intestinal CD103⁺CD11b⁺ DCs and a reci...

Significance Smad7 is a negative regulator of TGF-β signaling, a cytokine with anti-inflammatory properties. Although TGF-β was implicated in the development and function of dendritic cells (DCs), the in vivo role of Smad7 in DCs remains elusive. Here, we demonstrate that DC-specific Smad7 deletion affects the development of splenic CD8 ⁺ CD103 ⁺ D...

Dendritic cells (DC) are unique hematopoietic cells, linking innate and adaptive immune responses. In particular, they are considered as the most potent antigen presenting cells, governing both T cell immunity and tolerance. In view of their exceptional ability to present antigen and to interact with T cells, DC play distinct roles in shaping T cel...

Inflammation is part of a complex defense reaction of live tissues to injury. It is triggered by harmful stimuli, including pathogens, physical trauma, radiation, and chemical irritants. Inflammation is largely mediated by innate and adaptive immune cells in their efforts to eliminate the initial cause of tissue injury, clear out dead or infected c...

Skin dendritic cells (DC) are strategically positioned at the body's second largest epithelial border to the environment. Hence they are the first antigen presenting cells that encounter invading pathogens and environmental antigens, including contact sensitizers and carcinogens penetrating the skin. Moreover, DC have the unique ability to induce i...

In light of an enhanced awareness of ethical questions and ever increasing costs when working with animals in biomedical research, there is a dedicated and sometimes fierce debate concerning the (lack of) reproducibility of animal models and their relevance for human inflammatory diseases. Despite evident advancements in searching for alternatives,...

Supplementary Figures 1-12 and Supplementary Table 1

Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation....

Tissue immunosurveillance is an important mechanism to prevent cancer. Skin treatment with the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), followed by the tumor promoter 12-O-tetra-decanoyl-phorbol-13-acetate (TPA) is an established murine model for squamous cell carcinoma (SCC). However, the innate immunological events occurring during the i...

Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the identity of terminally differentiated cells are designat...

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in adaptive cell functions, and is highly active in the epidermis. AhR ligands can accelerate keratinocyte differentiation, but the precise role of AhR in the skin barrier is unknown. Our study showed that transepidermal water loss (TEWL), a parameter of skin ba...

Figure S1 (A–E) Numbers of CD4+ CD25+ FoxP3+ Tregs (A) and DC (B–E) in sdLNs in mice treated with ETOH or VIT D. Figure S2 Depletion of Langerin‐expressing DCs in epidermis (A–D) and sdLNs (E–H) from Langerin‐DTR mice, topically treated with ETOH (A, B, E and F) or VIT D (C, D, G and H), after intraperitoneal injection of PBS (A, C, E and G) or DT...

Although IL-10 promotes a regulatory phenotype of CD11c+ dendritic cells and macrophages in vitro, the role of IL-10 signaling in CD11c+ cells to maintain intestinal tolerance in vivo remains elusive. To this aim, we generated mice with a CD11c-specific deletion of the IL-10 receptor alpha (Cd11ccreIl10rafl/fl). In contrast to the colon, the small...

Atopic dermatitis (AD) is a widespread inflammatory skin disease with an early onset, characterized by pruritus, eczematous lesions and skin dryness. This chronic relapsing disease is believed to be primarily a result of a defective epidermal barrier function associated with genetic susceptibility, immune hyper-responsiveness of the skin and enviro...

Dendritic cells (DCs) are professional antigen presenting cells that have the dual ability to stimulate immunity and maintain tolerance. However, the signalling pathways mediating tolerogenic DC function in vivo remain largely unknown. The β-catenin pathway has been suggested to promote a regulatory DC phenotype. The aim of this study was to unrave...

Psoriasis is a common chronic inflammatory skin disease restricted to humans. The understanding of its pathogenesis has long been hampered by the lack of suitable chronic mouse models. The cytokine IL-17A has emerged as a key player in epithelial immune responses and the defense against extracellular pathogens. Moreover, enhanced expression of IL-1...

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has emerged as a crucial cytokine produced by auto-reactive T helper (Th) cells that initiate tissue inflammation. Multiple cell types can sense GM-CSF, but the identity of the pathogenic GM-CSF-responsive cells is unclear. By using conditional gene targeting, we systematically deleted the G...

Abbreviations: DC, dendritic cell; IFN, interferon; IL, interleukin; L. major, Leishmania major; sdLN, skin-draining lymph node; Th, T helper; Treg, regulatory T cell

Herpes simplex virus-type 1 (HSV-1) causes the majority of cutaneous viral infections. Viral infections are controlled by the immune system and CD8(+) cytotoxic T-lymphocytes (CTLs) have been shown to be crucial during the clearance of HSV-1 infections. Although epidermal Langerhans cells (LCs) are the first dendritic cells (DCs) getting into conta...

Recent findings have established that epidermal Langerhans cells (LCs) promote polyaromatic hydrocarbon (PAH)-induced carcinogenesis independent of their immunological properties by generating mutagenic PAH metabolites. In this issue, Girardi and colleagues (2014) extend their previous work and demonstrate that this mutagenic metabolism of LCs is i...

Skin is in daily contact with potentially harmful molecules from the environment such as cigarette smoke, automobile emissions, industrial soot and groundwater. Pregnane X receptor (PXR) is a transcription factor expressed in liver and intestine that is activated by xenobiotic chemicals including drugs and environmental pollutants. Topical applicat...