scholarly journals Quantification of dendritic cell subsets in human thymus tissues of various ages

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yan Li ◽  
Pei Chen ◽  
Hao Huang ◽  
Huiyu Feng ◽  
Hao Ran ◽  
...  

Abstract Background Dendritic cells (DCs) in the thymus are involved in central tolerance formation, but they also have other functions in the thymus, such as pathogen recognition. The density changes of human thymic DCs have been hardly investigated. In this study, human thymus samples of various ages were collected for tissue sectioning and staining. The thymic cortex and medulla area as well as the densities of various subsets of thymic DCs were calculated. Results All common DC subsets were found in the human thymus of various ages. Most DCs had accumulated in the human thymic epithelial space, especially the medulla. We also found that the human thymic cortex had atrophied relatively faster than the medulla, which led to a gradual increase of the area ratio of the medulla to cortex with the increase of age. The densities of DC subsets in the human thymus showed various changes with increasing age, which contributed to the composition changes of DC subsets. The density of plasmacytoid DCs (pDCs) in the human thymus had increased gradually with aging, which suggested that pDCs plays another essential role in the thymus in addition to central tolerance. Conclusions Inconsistent with the shrinking of the epithelial space in the thymus, the densities of DC subsets in the epithelial space of the thymus are maintained at a constant level with aging to preserve highly efficient autoreactive thymocyte screening. An increasing density of the thymic pDCs with aging implies an extra function of DCs in the thymus beyond central tolerance.

2021 ◽  
Author(s):  
Yan Li ◽  
Pei Chen ◽  
Hao Huang ◽  
Huiyu Feng ◽  
Hao Ran ◽  
...  

Abstract BackgroundDendritic cells (DCs) in the thymus are involved in central tolerance formation, but they also play other roles in the thymus. In this study, thymuses of different ages were collected for observation after tissue sectioning and staining. The area of cortex and medulla parts of the thymus in the sections and the density of different subsets of DCs in the thymus were also calculated. ResultsWe found that, along with the increasing age, the thymic cortex atrophies faster, leading to a gradual rise in the medullary's surface area ratio to that of the cortex with an increase in age. The medullary's surface area ratio to cortex can be used as an indirect reference to reflect the thymus hyperplasia. The density of DCs in the thymus showed different changes with the increasing age, and the density of plasmacytoid DCs (pDCs) in the thymus gradually increased with aging, suggesting that pDCs may play an essential role in the thymus in addition to central tolerance.ConclusionsThese findings complement our knowledge about the DCs’ subsets in the thymus along with physical ageing and help us understand the full function of DCs in the thymus beyond central tolerance.


Author(s):  
Meng Feng ◽  
Shuping Zhou ◽  
Yong Yu ◽  
Qinghong Su ◽  
Xiaofan Li ◽  
...  

Dendritic cells (DCs), a class of antigen-presenting cells, are widely present in tissues and apparatuses of the body, and their ability to migrate is key for the initiation of immune activation and tolerogenic immune responses. The importance of DCs migration for their differentiation, phenotypic states, and immunologic functions has attracted widespread attention. In this review, we discussed and compared the chemokines, membrane molecules, and migration patterns of conventional DCs, plasmocytoid DCs, and recently proposed DC subgroups. We also review the promoters and inhibitors that affect DCs migration, including the hypoxia microenvironment, tumor microenvironment, inflammatory factors, and pathogenic microorganisms. Further understanding of the migration mechanisms and regulatory factors of DC subgroups provides new insights for the treatment of diseases, such as infection, tumors, and vaccine preparation.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Noriaki Miyanaga ◽  
Hideaki Takagi ◽  
Tomofumi Uto ◽  
Tomohiro Fukaya ◽  
Junta Nasu ◽  
...  

AbstractWhile sublingual immunotherapy (SLIT) is known as an allergen-specific treatment for type-1 allergies, how it controls allergic pathogenesis remains unclear. Here, we show the prerequisite role of conventional dendritic cells in submandibular lymph nodes (ManLNs) in the effectiveness of SLIT for the treatment of allergic disorders in mice. Deficiency of conventional dendritic cells or CD4+Foxp3+ regulatory T (Treg) cells abrogates the protective effect of SLIT against allergic disorders. Furthermore, sublingual antigenic application primarily induces antigen-specific CD4+Foxp3+ Treg cells in draining ManLNs, in which it is severely impaired in the absence of cDCs. In ManLNs, migratory CD11b+ cDCs are superior to other conventional dendritic cell subsets for the generation of antigen-specific CD4+Foxp3+ Treg cells, which is reflected by their dominancy in the tolerogenic features to favor this program. Thus, ManLNs are privileged sites in triggering mucosal tolerance mediating protect effect of SLIT on allergic disorders that requires a tolerogenesis of migratory CD11b+ conventional dendritic cells.


2010 ◽  
Vol 40 (8) ◽  
pp. 2089-2094 ◽  
Author(s):  
Martin Guilliams ◽  
Sandrine Henri ◽  
Samira Tamoutounour ◽  
Laurence Ardouin ◽  
Isabelle Schwartz-Cornil ◽  
...  

2016 ◽  
Vol 213 (12) ◽  
pp. 2773-2791 ◽  
Author(s):  
Jesus Zamora-Pineda ◽  
Ashok Kumar ◽  
Jung H. Suh ◽  
Meng Zhang ◽  
Julie D. Saba

T cell egress from the thymus is essential for adaptive immunity and involves chemotaxis along a sphingosine-1-phosphate (S1P) gradient. Pericytes at the corticomedullary junction produce the S1P egress signal, whereas thymic parenchymal S1P levels are kept low through S1P lyase (SPL)–mediated metabolism. Although SPL is robustly expressed in thymic epithelial cells (TECs), in this study, we show that deleting SPL in CD11c+ dendritic cells (DCs), rather than TECs or other stromal cells, disrupts the S1P gradient, preventing egress. Adoptive transfer of peripheral wild-type DCs rescued the egress phenotype of DC-specific SPL knockout mice. These studies identify DCs as metabolic gatekeepers of thymic egress. Combined with their role as mediators of central tolerance, DCs are thus poised to provide homeostatic regulation of thymic export.


2007 ◽  
Vol 2007 ◽  
pp. 1-7 ◽  
Author(s):  
Aldona Pietrzak ◽  
Konrad Janowski ◽  
Grażyna Chodorowska ◽  
Anna Michalak-Stoma ◽  
Jacek Rolinski ◽  
...  

Peripheral blood dendritic cells seem to play a crucial role in psoriatic inflammatory processes. The aim of our study is to investigate the relationship between plasma interleukin-18 (IL-18) levels and blood dendritic cells in psoriatic patients. IL-18 plasma levels were measured by ELISA. Phenotypes of dendritic cell subsets were analyzed by double-colour flow cytometry. Plasma IL-18 level in psoriatic males was significantly higher, whereas counts of BDCA-2+ cells were lower than in the control group. The myeloid/plasmacytoid ratio was significantly higher in the patient group compared to the control one. In the patient group, significant negative correlations between plasma IL-18 level and both the BDCA-1+ and BDCA-2+ counts were found. BDCA-1+ counts correlated negatively with percentage of skin involvement. IL-18 seems to play a role in psoriasis pathogenesis. The decreased counts of blood plasmacytoid DCs in psoriatic patients might result from IL-18 down-regulation of plasmacytoid DC precursor proliferation.


2021 ◽  
Vol 219 (2) ◽  
Author(s):  
David A. Anderson ◽  
Feiya Ou ◽  
Sunkyung Kim ◽  
Theresa L. Murphy ◽  
Kenneth M. Murphy

During dendritic cell (DC) development, Myc expression in progenitors is replaced by Mycl in mature DCs, but when and how this transition occurs is unknown. We evaluated DC development using reporters for MYC, MYCL, and cell cycle proteins Geminin and CDT1 in wild-type and various mutant mice. For classical type 1 dendritic cells (cDC1s) and plasmacytoid DCs (pDCs), the transition occurred upon their initial specification from common dendritic cell progenitors (CDPs) or common lymphoid progenitors (CLPs), respectively. This transition required high levels of IRF8 and interaction with PU.1, suggesting the use of EICEs within Mycl enhancers. In pDCs, maximal MYCL induction also required the +41kb Irf8 enhancer that controls pDC IRF8 expression. IRF8 also contributed to repression of MYC. While MYC is expressed only in rapidly dividing DC progenitors, MYCL is most highly expressed in DCs that have exited the cell cycle. Thus, IRF8 levels coordinate the Myc-Mycl transition during DC development.


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