scholarly journals Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation

2018 ◽  
Vol 215 (2) ◽  
pp. 481-500 ◽  
Author(s):  
Tal Capucha ◽  
Noam Koren ◽  
Maria Nassar ◽  
Oded Heyman ◽  
Tsipora Nir ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Differentiation ◽  
Lamina Propria ◽  
Langerhans Cells ◽  
Tissue Destruction ◽  
Step Process ◽  
Mucosal Homeostasis ◽  
Tgf Β1

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 epithelium. Within the epithelium, TGF-β1 finalizes LC differentiation, and ALK5 is crucial to this process. Moreover, the local microbiota has a major impact on the development of mucosal LCs, whereas LCs in turn maintain mucosal homeostasis and prevent tissue destruction. These results reveal the differential and sequential role of TGF-β1 and BMP7 in LC differentiation and highlight the intimate interplay of LCs with the microbiota.

Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γ production and the induction of Th1 cell differentiation

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 553-560 ◽  
Author(s):  
Naoki Tokumasa ◽  
Akira Suto ◽  
Shin-ichiro Kagami ◽  
Shunsuke Furuta ◽  
Koichi Hirose ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Differentiation ◽  
Cpg Odn ◽  
T Helper ◽  
Dc Functions ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Ifn Γ ◽  
Antigen Presenting

Abstract It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper–cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2−/−) mice, IL-12–induced Stat4 phosphorylation was diminished in Tyk2−/− DCs. IL-12–induced IFN-γ production was also significantly diminished in Tyk2−/− DCs to levels similar to those in Stat4−/− DCs. Interestingly, Tyk2−/− DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2−/− DCs were impaired in their ability to induce Th1-cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN-γ from DCs and thereby for the induction of antigen-specific Th1-cell differentiation.

Role Of Lamina Propria Dendritic Cells In Translating Murine Norovirus Infection Into Atopic Disease

2010 ◽  
Vol 125 (2) ◽  
pp. AB193
Author(s):  
X. Chen ◽  
D. Leach ◽  
S.J. Ehlenbach ◽  
M.H. Grayson
Keyword(s):  
Dendritic Cells ◽  
Lamina Propria ◽  
Atopic Disease ◽  
Murine Norovirus

Role of Langerhans cells and other dendritic cells in viral diseases

1993 ◽  
Vol 132 (1-2) ◽  
pp. 1-28 ◽  
Author(s):  
E. Sprecher ◽  
Y. Becker
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cells ◽  
Viral Diseases

scholarly journals Specific Protein Antigen Delivery to Human Langerhans Cells in Intact Skin

2021 ◽  
Vol 12 ◽  
Author(s):  
Mareike Rentzsch ◽  
Robert Wawrzinek ◽  
Claudia Zelle-Rieser ◽  
Helen Strandt ◽  
Lydia Bellmann ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cells ◽  
Specific Protein ◽  
Protein Antigen ◽  
Antigen Delivery ◽  
Model Protein ◽  
Skin Explants ◽  
Antigen Presenting ◽  
Target Effects

Immune modulating therapies and vaccines are in high demand, not least to the recent global spread of SARS-CoV2. To achieve efficient activation of the immune system, professional antigen presenting cells have proven to be key coordinators of such responses. Especially targeted approaches, actively directing antigens to specialized dendritic cells, promise to be more effective and accompanied by reduced payload due to less off-target effects. Although antibody and glycan-based targeting of receptors on dendritic cells have been employed, these are often expensive and time-consuming to manufacture or lack sufficient specificity. Thus, we applied a small-molecule ligand that specifically binds Langerin, a hallmark receptor on Langerhans cells, conjugated to a model protein antigen. Via microneedle injection, this construct was intradermally administered into intact human skin explants, selectively loading Langerhans cells in the epidermis. The ligand-mediated cellular uptake outpaces protein degradation resulting in intact antigen delivery. Due to the pivotal role of Langerhans cells in induction of immune responses, this approach of antigen-targeting of tissue-resident immune cells offers a novel way to deliver highly effective vaccines with minimally invasive administration.

Compensatory role of Langerhans cells and langerin-positive dermal dendritic cells in the sensitization phase of murine contact hypersensitivity

2010 ◽  
Vol 125 (5) ◽  
pp. 1154-1156.e2 ◽  
Author(s):  
Tetsuya Honda ◽  
Saeko Nakajima ◽  
Gyohei Egawa ◽  
Kouetsu Ogasawara ◽  
Bernard Malissen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cells ◽  
Contact Hypersensitivity ◽  
Sensitization Phase
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