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Cellular & Molecular Immunology May 2014Thymic microenvironments are essential for the maturation of thymocytes, which can be anatomically compartmentalized into cortical and medullar regions. The absence of...
Thymic microenvironments are essential for the maturation of thymocytes, which can be anatomically compartmentalized into cortical and medullar regions. The absence of the gene encoding the transcription factor forkhead box n1 (Foxn1) causes epithelial differentiation to stall in the precursor stage, resulting in the formation of an abnormal thymus. In this study, we used human umbilical cord-derived mesenchymal stem cells (UC-MSCs) to treat Foxn1(-/-) mice, and then analyzed the maturation and distribution of thymic epithelial cells in the Foxn1(-/-) thymic rudiment and the thymopoiesis of this newly developed rudiment. Our data showed a well-organized cortex-medulla architecture and an obvious improvement in the maturation of thymic epithelial cells along with the appearance of UEA-1(+)MHCII(hi) thymic epithelial cells in the rudiment. We further demonstrated improved thymopoiesis and the enhanced export of mature T cells with increased numbers of regulatory T cells into the peripheral blood. Furthermore, we observed that MSCs can engraft into thymic tissue and express many cytokines or proteins, particularly keratinocyte growth factor (KGF) and CD248, which are essential for thymic development. Collectively, our data identified a new mechanism for MSCs, which may provide a proper microenvironment for the reconstitution and functional maturation of the thymus in Foxn1(-/-) mice. Additionally, we elicited additional insights into the therapeutic efficacy of MSCs in several autoimmune diseases.
Topics: Animals; Cell Count; Cell Differentiation; Cell Separation; Cytokines; Epithelial Cells; Forkhead Transcription Factors; Humans; Intercellular Signaling Peptides and Proteins; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; T-Lymphocytes, Regulatory; Thymus Gland; Umbilical Cord
PubMed: 24561455
DOI: 10.1038/cmi.2013.69 -
Medicine Nov 2022Lipofibroadenoma is an extremely rare thymic tumor, and the anterior mediastinum is the most common site.
BACKGROUND
Lipofibroadenoma is an extremely rare thymic tumor, and the anterior mediastinum is the most common site.
CASE SUMMARY
A 21-year-old male was admitted with fever without obvious cause for 2 months. After admission, the patient's highest temperature was 38.3°C, accompanied by diarrhea. Physical examination showed coarse breath sounds in both lungs. Chest enhanced computed tomography (CT) showed a mass of mixed density shadow on the left side of the anterior mediastinum with a size of approximately 9.2 cm × 5 cm × 2.1 cm and a clear boundary mixed with a low fat density shadow. Mediastinal tumors were removed under general anesthesia by video-assisted thoracoscopic surgery. Macroscopically, a clear boundary was shown between the tumor and the remaining thymus. Microscopically, the tumor contained a large amount of mature adipose and fibrous tissue with scattered cord-like epithelial tissue and a small number of lymphocytes scattered in the stroma. The tumor lacked thymic bodies. The neoplastic epithelial cells were oval or polygonal and arranged in fissures, the nuclei were uniform in size and mild in shape, and mitosis was rare. Epithelial cells were positive for AE1/AE3 and CK19, lymphocytes were positive for CD3 and CD20, and fat and fibrous tissue were positive for S-100 and vimentin, respectively. The Ki67 labeling index was less than 5%. Based on histological features and immunophenotype, thymic lipofibroadenoma was diagnosed. The patient was followed up 1 year after the operation, and no recurrence or residual lesions were found on the X-ray re-examination.
CONCLUSION
Lipofibroadenoma is a benign thymic tumor, and thymectomy is regarded as the best treatment. The biological behavior of thymic lipofibroadenoma is good, and the recurrence rate is low.
Topics: Humans; Male; Young Adult; Adult; Mediastinum; Thymoma; Thymus Neoplasms; Thymectomy; Mediastinal Neoplasms
PubMed: 36401401
DOI: 10.1097/MD.0000000000031732 -
Blood Nov 2014Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells for patients without HLA-matched adult donors. UCB contains a low number of nucleated... (Review)
Review
Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells for patients without HLA-matched adult donors. UCB contains a low number of nucleated cells and mostly naive T cells, resulting in prolonged time to engraftment and lack of transferred T-cell memory. Although the first phase of T-cell reconstitution after UCB transplantation (UCBT) depends on peripheral expansion of transferred T cells, permanent T-cell reconstitution is mediated via a central mechanism, which depends on de novo production of naive T lymphocytes by the recipient's thymus from donor-derived lymphoid-myeloid progenitors (LMPs). Thymopoiesis can be assessed by quantification of recent thymic emigrants, T-cell receptor excision circle levels, and T-cell receptor repertoire diversity. These assays are valuable tools for monitoring posttransplantation thymic recovery, but more importantly they have shown the significant prognostic value of thymic reconstitution for clinical outcomes after UCBT, including opportunistic infections, disease relapse, and overall survival. Strategies to improve thymic entry and differentiation of LMPs and to accelerate recovery of the thymic stromal microenvironment may improve thymic lymphopoiesis. Here, we discuss the mechanisms and clinical implications of thymic recovery and new approaches to improve reconstitution of the T-cell repertoire after UCBT.
Topics: Adult; Animals; Cell Differentiation; Cell Proliferation; Cord Blood Stem Cell Transplantation; Humans; Lymphopoiesis; T-Lymphocytes; Thymus Gland; Transplantation, Homologous; Treatment Outcome
PubMed: 25287708
DOI: 10.1182/blood-2014-07-589176 -
Annals of Cardiothoracic Surgery Mar 2023Robotic-assisted surgery for mediastinal disease has been shown to be beneficial in facilitating easier mediastinal dissection with its three-dimensional views and...
BACKGROUND
Robotic-assisted surgery for mediastinal disease has been shown to be beneficial in facilitating easier mediastinal dissection with its three-dimensional views and multi-articulated moving instruments. Herein, we report our experience with the biportal approach of robot-assisted anterior mediastinal mass surgery, including both lateral transthoracic and subxiphoid approaches.
METHODS
We retrospectively analyzed 21 patients who underwent biportal robotic-assisted anterior mediastinal mass resection, without considering the tumor size between May 2018 and September 2022. We reviewed the technical advantages and limitations of the biportal approach and the perioperative outcomes, including operative time, conversion to multiport or open surgery, duration of chest drainage, and postoperative complications, to define the role of robot-assisted surgery using the biportal approach.
RESULTS
We approached the thoracic cavity from the right side in five patients, from the left side in three patients, and from the subxiphoid in 13 patients. Thymomas (n=13) and thymic cysts (n=3) were the most common diagnoses. The median operative time was 165 min [interquartile range (IQR), 140-196 min]. There were no conversions to multiport or open surgery. The chest drain was removed at a median of two days (IQR, 1-3 days), and the patients were discharged at a median of four days (IQR, 3-5 days). Perioperative complications were reported in two patients (one with prolonged air leak and one with vocal cord palsy). There were no cases of readmission or delayed complication.
CONCLUSIONS
The biportal approach for robot-assisted surgery in anterior mediastinal masses is a feasible and safe alternative for treating associated pathologies. The subxiphoid approach for mediastinal surgery provides a better surgical view than the transthoracic approach. The biportal approach also enables the use of robotic staplers and energy devices and minimizes instrumental interference compared to that in the single-port approach.
PubMed: 37035644
DOI: 10.21037/acs-2022-urats-24 -
BioRxiv : the Preprint Server For... Apr 2023Within the thymus, regulation of the cellular cross-talk directing T cell development is dependent on spatial interactions within specialized niches. To create a...
Within the thymus, regulation of the cellular cross-talk directing T cell development is dependent on spatial interactions within specialized niches. To create a holistic, spatially defined map of tissue niches guiding postnatal T cell development we employed the multidimensional imaging platform CO-detection by indEXing (CODEX), as well as CITE-seq and ATAC-seq. We generated age-matched 4-5-month-old postnatal thymus datasets for male and female donors, and identify significant sex differences in both T cell and thymus biology. We demonstrate a crucial role for JAG ligands in directing thymic-like dendritic cell development, reveal important functions of a novel population of ECM fibroblasts, and characterize the medullary niches surrounding Hassall's corpuscles. Together, these data represent a unique age-matched spatial multiomic resource to investigate how sex-based differences in thymus regulation and T cell development arise, and provide an essential resource to understand the mechanisms underlying immune function and dysfunction in males and females.
PubMed: 37090676
DOI: 10.1101/2023.04.13.536804 -
Frontiers in Immunology 2018Mice engrafted with human immune cells offer powerful model systems to investigate molecular and cellular processes of tumorigenesis, as well as to test therapeutic... (Review)
Review
Mice engrafted with human immune cells offer powerful model systems to investigate molecular and cellular processes of tumorigenesis, as well as to test therapeutic approaches to treat the resulting cancer. The use of umbilical cord blood mononuclear cells as a source of human immune cells for engraftment is technically straightforward, and provides T lymphocytes and autologous antigen-presenting cells (including B cells, monocytes, and DCs) that bear cognate antigen presenting molecules. By using a human-specific oncogenic virus, such as Epstein-Barr virus, neoplastic transformation of the human B cells can be induced in a manner that models progressive stages of tumorigenesis from nascent neoplasia to the establishment of vascularized tumor masses with an immunosuppressive environment. Moreover, since tumorigenesis occurs in the presence of autologous T cells, this type of system can be used to investigate how T cells become suppressed during tumorigenesis, and how immunotherapies counteract immunosuppression. This minireview will provide a brief overview of the use of human umbilical cord blood transplanted into immunodeficient murine hosts to model antitumor responses.
Topics: Animals; Blood Transfusion; Disease Models, Animal; Fetal Blood; Graft Survival; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Immunotherapy; Lymphocyte Activation; Mice; Neoplasms; T-Lymphocytes; Thymus Gland; Xenograft Model Antitumor Assays
PubMed: 29434589
DOI: 10.3389/fimmu.2018.00054 -
Neurochemical Research Dec 2022Neuropathic pain is a debilitating chronic disorder, significantly causing personal and social burdens, in which activated neuroinflammation is one major contributor....
Neuropathic pain is a debilitating chronic disorder, significantly causing personal and social burdens, in which activated neuroinflammation is one major contributor. Thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33 is important for chronic inflammation. Linalyl acetate (LA) is main component of lavender oil with an anti-inflammatory property through TSLP signaling. The aim of the study is to investigate how LA regulates mechanical hyperalgesia after sciatic nerve injury (SNI). Adult Sprague-Dawley male rats were separated into 3 groups: control group, SNI group and SNI with LA group. LA was administrated intraperitoneally one day before SNI. Pain behavior test was evaluated through calibration forceps testing. Ipsilateral sciatic nerves (SNs), dorsal root ganglions (DRGs) and spinal cord were collected for immunofluorescence staining and Western blotting analyses. SNI rats were more sensitive to hyperalgesia response to mechanical stimulus since operation, which was accompanied by spinal cord glial cells reactions and DRG neuro-glial interaction. LA could relieve the pain sensation, proinflammatory cytokines and decrease the expression of TSLP/TSLPR complex. Also, LA could reduce inflammation through reducing IL-33 signaling. This study is the first to indicate that LA can modulate pain through TSLP/TSLPR and IL-33 signaling after nerve injury.
Topics: Male; Rats; Animals; Hyperalgesia; Interleukin-33; Rats, Sprague-Dawley; Cytokines; Neuralgia; Peripheral Nerve Injuries; Sciatic Neuropathy; Inflammation; Thymic Stromal Lymphopoietin
PubMed: 36287299
DOI: 10.1007/s11064-022-03763-1 -
Journal of Occupational and... Oct 2016We aimed to determine whether average and trimester-specific exposures to ambient measures of nitrogen dioxide (NO2) and particular matter (PM2.5) were associated with...
OBJECTIVES
We aimed to determine whether average and trimester-specific exposures to ambient measures of nitrogen dioxide (NO2) and particular matter (PM2.5) were associated with elevated cord blood concentrations of immunoglobulin E (IgE) and two epithelial cell produced cytokines: interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP).
METHODS
This study utilized data and biospecimens from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. There were 2001 pregnant women recruited between 2008 and 2011 from 10 Canadian cities. Maternal exposure to NO2 and PM2.5 was estimated using land use regression and satellite-derived models.
RESULTS
We observed statistically significant associations between maternal NO2 exposure and elevated cord blood concentrations of both IL-33 and TSLP among girls but not boys.
CONCLUSIONS
Maternal NO2 exposure may impact the development of the newborn immune system as measured by cord blood concentrations of two cytokines.
Topics: Air Pollution; Biomarkers; Canada; Cities; Cytokines; Female; Fetal Blood; Humans; Immune System; Immunoglobulin E; Infant, Newborn; Interleukin-33; Male; Maternal Exposure; Nitric Oxide; Nitrogen Dioxide; Particulate Matter; Pregnancy; Thymic Stromal Lymphopoietin
PubMed: 27483336
DOI: 10.1097/JOM.0000000000000841 -
Aging Sep 2020To study the effect of allogeneic umbilical cord mesenchymal stem cell transplantation on the structure and function of the thymus in aged C57 mice and provide a new...
Umbilical cord mesenchymal stem cells protect thymus structure and function in aged C57 mice by downregulating aging-related genes and upregulating autophagy- and anti-oxidative stress-related genes.
BACKGROUND
To study the effect of allogeneic umbilical cord mesenchymal stem cell transplantation on the structure and function of the thymus in aged C57 mice and provide a new method for the treatment of senile thymic atrophy.
RESULTS
The changes in the thymus cortex and medulla volume and the lymphocyte ratio were analyzed by immunofluorescence. For thymus tissue sections, immunohistochemical staining was performed to detect p16, p53, SOD, becline1, LC3b, p62, sirt1, and sirt3. Changes in CK5, CK8, CD4 and CD8 expression were observed. Treatment with mUCMSCs could promote hair regeneration in aging mice and regenerate the thymus structure.
CONCLUSIONS
mUCMSCs inhibited senescence of the thymus and promoted structural and functional thymus regeneration by downregulating the senescence genes p53 and p16 and upregulating the SOD, Sirt1 and Sirt3 genes, but the mechanism requires further research.
METHODS
C57 mice were obtained and met the requirements of thymic aging. mUCMSCs were infused via the tail vein at a dose of 1×10 cells/kg twice per week for 3 weeks. Six weeks after the last transplantation, the thymus was weighed, and the thymus-to-body weight ratio was calculated. The thymus tissue was stained with HE.
PubMed: 32924972
DOI: 10.18632/aging.103594 -
International Journal of Hygiene and... Jul 2016Triclosan is widely used as an antimicrobial agent and preservative that has been hypothesized to play a role in asthma and allergic disease. The limited body of...
Triclosan is widely used as an antimicrobial agent and preservative that has been hypothesized to play a role in asthma and allergic disease. The limited body of literature regarding the allergenicity of triclosan has not evaluated prenatal exposure and subsequent potential effects on the developing immune system. The objective of the present study was to determine the association between prenatal urinary triclosan concentrations and cord blood immune system biomarker concentrations. Umbilical cord blood samples were obtained from the Maternal-Infant Research on Environmental Chemicals (MIREC) Biobank and were tested for three immune system biomarkers: immunoglobulin E (IgE), thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33). Triclosan concentrations were measured in urine at 6-13 weeks gestation. No statistically significant associations were observed between prenatal triclosan concentrations and elevated concentrations of any immune system biomarker (n=1219 participants). Longitudinal studies are necessary to determine how the observed findings at birth translate into childhood.
Topics: Adult; Anti-Infective Agents, Local; Biomarkers; Cytokines; Environmental Monitoring; Environmental Pollutants; Female; Fetal Blood; Humans; Immunoglobulin E; Interleukin-33; Maternal Exposure; Odds Ratio; Pregnancy; Triclosan; Thymic Stromal Lymphopoietin
PubMed: 27167448
DOI: 10.1016/j.ijheh.2016.04.010