scholarly journals The Role of AIRE Deficiency in Infertility and Its Potential Pathogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xueyang Zou ◽  
Yi Zhang ◽  
Xiaoya Wang ◽  
Rongchao Zhang ◽  
Wei Yang
Keyword(s):  
Immune Responses ◽  
Germ Cells ◽  
Ovarian Function ◽  
Thymic Epithelial Cells ◽  
Number Of Patients ◽  
Age Dependent ◽  
Medullary Thymic Epithelial Cells ◽  
Specific Antigens ◽  
Insight Into

The increasing number of patients with infertility is recognized as an emerging problem worldwide. However, little is known about the cause of infertility. At present, it is believed that infertility may be related to genetic or abnormal immune responses. It has long been indicated that autoimmune regulator (AIRE), a transcription factor, participates in immune tolerance by regulating the expression of thousands of promiscuous tissue-specific antigens in medullary thymic epithelial cells (mTECs), which play a pivotal role in preventing autoimmune diseases. AIRE is also expressed in germ cell progenitors. Importantly, the deletion of AIRE leads to severe oophoritis and age-dependent depletion of follicular reserves and causes altered embryonic development in female mice. AIRE-deficient male mice exhibit altered apoptosis during spermatogenesis and have a significantly decreased breeding capacity. These reports suggest that AIRE deficiency may be responsible for infertility. The causes may be related to the production of autoantibodies against sperm, poor development of germ cells, and abnormal ovarian function, which eventually lead to infertility. Here, we focus on the potential associations of AIRE deficiency with infertility as well as the possible pathogenesis, providing insight into the significance of AIRE in the development of infertility.

scholarly journals Resolution of primary hyperparathyroidism following surgical removal of cervical thymus

2017 ◽  
Vol 4 (2) ◽  
pp. 5
Author(s):  
Rossella Cannarella ◽  
Beniamino Scilletta ◽  
Roberto Scilletta ◽  
Gaetano Magro ◽  
Aldo E. Calogero
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Single Case ◽  
Thymic Epithelial Cells ◽  
Surgical Removal ◽  
Thymus Tissue ◽  
Medullary Thymic Epithelial Cells ◽  
Serum Pth ◽  
Thymus Cells

Recent research has emphasized the capacity of thymus cells of producing parathyroid hormone (PTH) if adequately stimulated, and have investigated the role of the so-called “thymic PTH”, produced by the medullary thymic epithelial cells (m-TECs). To the best of our knowledge, only a single case of well-documented PTH secretion from a thymoma causing primary hyperparathyroidism (PHTP) has been reported in the literature so far. We report here the case of a female patient with PHTP who underwent neck exploration for a suspected parathyroid adenoma. After surgery, a normalization of serum PTH concentration was observed, but the histological examination of the surgically excised mass revealed exclusively normal thymus tissue. The present case provides additional evidence of PHTP caused by an ectopic thymus. 

Integrative analysis of scRNAs-seq and scATAC-seq revealed transit-amplifying thymic epithelial cells expressing autoimmune regulator

2021 ◽  
Author(s):  
Takahisa Miyao ◽  
Maki Miyauchi ◽  
S. Thomas Kelly ◽  
Tommy W. Terooatea ◽  
Tatsuya Ishikawa ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Single Cell ◽  
Tolerance Induction ◽  
Integrative Analysis ◽  
Thymic Epithelial Cells ◽  
Self Tolerance ◽  
Cell Assays ◽  
Medullary Thymic Epithelial Cells ◽  
Specific Antigens ◽  
Accessible Chromatin

SummaryMedullary thymic epithelial cells (mTECs) are critical for self-tolerance induction in T cells via promiscuous expression of tissue-specific antigens (TSAs), which are controlled by transcriptional regulator AIRE. Whereas AIRE-expressing (Aire+) mTECs undergo constant turnover in the adult thymus, mechanisms underlying differentiation of postnatal mTECs remain to be discovered. Integrative analysis of single-cell assays for transposase accessible chromatin (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) suggested the presence of proliferating mTECs with a specific chromatin structure, which express high levels of Aire and co-stimulatory molecules CD80 (Aire+CD80hi). Proliferating Aire+CD80hi mTECs detected by using Fucci technology express a minimal level of Aire-dependent TSAs and are converted into quiescent Aire+CD80hi mTECs expressing high levels of TSAs after a transit amplification. These data provide evidence for the existence of transit amplifying Aire+mTEC precursors during Aire+mTEC differentiation process of the postnatal thymus.

scholarly journals What We Know So Far about the Metabolite-Mediated Microbiota-Intestinal Immunity Dialogue and How to Hear the Sound of This Crosstalk

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 406
Author(s):  
Clément Caffaratti ◽  
Caroline Plazy ◽  
Geoffroy Mery ◽  
Abdoul-Razak Tidjani ◽  
Federica Fiorini ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Immune Cells ◽  
Causal Effect ◽  
Host Immunity ◽  
Intestinal Immunity ◽  
Host Health ◽  
Membrane Bound ◽  
Insight Into

Trillions of microorganisms, termed the “microbiota”, reside in the mammalian gastrointestinal tract, and collectively participate in regulating the host phenotype. It is now clear that the gut microbiota, metabolites, and intestinal immune function are correlated, and that alterations of the complex and dynamic host-microbiota interactions can have deep consequences for host health. However, the mechanisms by which the immune system regulates the microbiota and by which the microbiota shapes host immunity are still not fully understood. This article discusses the contribution of metabolites in the crosstalk between gut microbiota and immune cells. The identification of key metabolites having a causal effect on immune responses and of the mechanisms involved can contribute to a deeper insight into host-microorganism relationships. This will allow a better understanding of the correlation between dysbiosis, microbial-based dysmetabolism, and pathogenesis, thus creating opportunities to develop microbiota-based therapeutics to improve human health. In particular, we systematically review the role of soluble and membrane-bound microbial metabolites in modulating host immunity in the gut, and of immune cells-derived metabolites affecting the microbiota, while discussing evidence of the bidirectional impact of this crosstalk. Furthermore, we discuss the potential strategies to hear the sound of such metabolite-mediated crosstalk.

scholarly journals Sirt6 Regulates the Development of Medullary Thymic Epithelial Cells and Contributes to the Establishment of Central Immune Tolerance

2021 ◽  
Vol 9 ◽  
Author(s):  
Qian Zhang ◽  
Zhanfeng Liang ◽  
Jiayu Zhang ◽  
Tong Lei ◽  
Xue Dong ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Conditional Knockout ◽  
Thymic Epithelial Cells ◽  
Reduced Body ◽  
Epigenetic Regulator ◽  
Development And Differentiation ◽  
Medullary Thymic Epithelial Cells ◽  
Proliferation Ability ◽  
Made In

Although some advances have been made in understanding the molecular regulation of mTEC development, the role of epigenetic regulators in the development and maturation of mTEC is poorly understood. Here, using the TEC-specific Sirt6 knockout mice, we found the deacetylase Sirtuin 6 (Sirt6) is essential for the development of functionally competent mTECs. First of all, TEC-specific Sirt6 deletion dramatically reduces the mTEC compartment, which is caused by reduced DNA replication and subsequent impaired proliferation ability of Sirt6-deficient mTECs. Secondly, Sirt6 deficiency specifically accelerates the differentiation of mTECs from CD80–Aire– immature population to CD80+Aire– intermediate mature population by promoting the expression of Spib. Finally, Sirt6 ablation in TECs markedly interferes the proper expression of tissue-restricted antigens (TRAs) and impairs the development of thymocytes and nTreg cells. In addition, TEC conditional knockout of Sirt6 results in severe autoimmune disease manifested by reduced body weight, the infiltration of lymphocytes and the presence of autoantibodies. Collectively, this study reveals that the expression of epigenetic regulator Sirt6 in TECs is crucial for the development and differentiation of mTECs, which highlights the importance of Sirt6 in the establishment of central immune tolerance.

Extrathymic Aire-expressing cells support maternal-fetal tolerance

2021 ◽  
Vol 6 (61) ◽  
pp. eabf1968
Author(s):  
Eva Gillis-Buck ◽  
Haleigh Miller ◽  
Marina Sirota ◽  
Stephan J. Sanders ◽  
Vasilis Ntranos ◽  
...  
Keyword(s):  
Thymic Epithelial Cells ◽  
Activated T Cells ◽  
Healthy Pregnancy ◽  
Follicular Helper ◽  
Immune Mediated ◽  
Self Tolerance ◽  
Selective Ablation ◽  
Medullary Thymic Epithelial Cells ◽  
Early Mouse

Healthy pregnancy requires tolerance to fetal alloantigens as well as syngeneic embryonic and placental antigens. Given the importance of the autoimmune regulator (Aire) gene in self-tolerance, we investigated the role of Aire-expressing cells in maternal-fetal tolerance. We report that maternal ablation of Aire-expressing (Aire+) cells during early mouse pregnancy caused intrauterine growth restriction (IUGR) in both allogeneic and syngeneic pregnancies. This phenotype is immune mediated, as IUGR was rescued in Rag1-deficient mice, and involved a memory response, demonstrated by recurrence of severe IUGR in second pregnancies. Single-cell RNA sequencing demonstrated that Aire+ cell depletion in pregnancy results in expansion of activated T cells, particularly T follicular helper cells. Unexpectedly, selective ablation of either Aire-expressing medullary thymic epithelial cells or extrathymic Aire-expressing cells (eTACs) mapped the IUGR phenotype exclusively to eTACs. Thus, we report a previously undescribed mechanism for the maintenance of maternal-fetal immune homeostasis and demonstrate that eTACs protect the conceptus from immune-mediated IUGR.

The role of cytokines in both the normal and malignant ovary.

1999 ◽  
pp. 93-107 ◽  
Author(s):  
M A Nash ◽  
G Ferrandina ◽  
M Gordinier ◽  
A Loercher ◽  
R S Freedman
Keyword(s):  
Immune Responses ◽  
Growth Regulation ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Rapid Development ◽  
Therapeutic Approaches ◽  
Normal Tissues ◽  
Cytokines And Chemokines ◽  
Normal Ovarian Tissue

Normal ovarian tissue is rich in cytokines. Cytokines and chemokines are important in the physiology of ovarian function and of ovulation. Cytokines and chemokines may recruit cytokine-producing lymphocytes to the site of a developing follicle, and cytokines appear to play an important role in pre and post follicle development. Most of the same cytokines that are found in normal ovarian tissue are also found in association with malignancy in contrast to their functions in normal tissues. It is reasonable to assume that the functions of cytokines associated with malignancy may serve to promote the unregulated growth if tumor cells and metastasis. It is also likely that cytokines produced by tumors will modulate immune responses that favor tumor progression. In the following review, we have highlighted those functions of cytokines that have been identified as having the most significant impact on tumor growth and development. By examining activities of these cytokines in normal and in malignant ovarian tissues, it is hoped that future possible avenues for investigation may be opened up and that the results of these investigations will lead to strategies that can modulate the production or the activity of the cytokines leading to the growth of tumors or their metastases. Such strategies now fall under the general discipline of bioimmunotherapy. This is an expanding discipline as more is learned about growth regulation in cancer, and with the availability and rapid development of new molecules for therapeutic approaches.

scholarly journals Role of Microbiome in Modulating Immune Responses in Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Mukulika Bose ◽  
Pinku Mukherjee
Keyword(s):  
Environmental Factors ◽  
Immune Responses ◽  
Disease Susceptibility ◽  
Cancer Susceptibility ◽  
Cancer Development ◽  
Complex Interactions ◽  
Gene Environment ◽  
Mechanisms Of Carcinogenesis ◽  
Insight Into

The complex interactions between genes and the environment play important roles in disease susceptibility and progression. One of the chronic diseases that is affected by this gene-environment interplay is cancer. However, our knowledge about these environmental factors remains limited. The microorganisms that inhabit our bodies have recently been acknowledged to play a crucial role as an environmental factor, to which we are constantly exposed. Studies have revealed significant differences in the relative abundance of certain microbes in cancer cases compared with controls. It has been reported that changes in the composition of normal gut microbiota can increase/decrease cancer susceptibility and progression by diverse mechanisms including, but not limited to, inflammation—a well-known hallmark of carcinogenesis. The microbiota can also affect the response to various treatments including immunotherapy. The microbiome-immune-cancer axis will continue to provide insight into the basic mechanisms of carcinogenesis. In this review, we provide a brief understanding of the mechanisms by which microbiota affects cancer development, progression, and treatment.

scholarly journals Microarray analysis reveals the role of matrix metalloproteinases in mouse experimental autoimmune myocarditis induced by cardiac myosin peptides

2007 ◽  
Vol 12 (2) ◽  
Author(s):  
Qizhu Tang ◽  
Ji Huang ◽  
Haiyan Qian ◽  
Ran Xiong ◽  
Difei Shen ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Microarray Analysis ◽  
Molecular Mechanisms ◽  
Global Changes ◽  
Autoimmune Myocarditis ◽  
Molecular Events ◽  
Specific Antigens ◽  
Experimental Mouse ◽  
Insight Into

AbstractAutoimmune myocarditis develops after the presentation of heart-specific antigens to autoaggressive CD4+ T cells and after inflammation has infiltrated the tissues. To shed light on global changes in the gene expression of autoimmune myocarditis and to gain further insight into the molecular mechanisms underlying the genesis of myocarditis, we conducted a comprehensive microarray analysis of mRNA using an experimental mouse autoimmune myocarditis model via immunization with α-myosin heavy chain-derived peptides. Of over 39,000 transcripts on a high density oligonucleotide microarray, 466 were under-expressed and 241 over-expressed by ≥ 1.5-fold compared with the controls in BALB/C mouse with autoimmune myocarditis. In this paper, we list the top 50 up-regulated genes related to the immune response. These altered genes encode for leukocyte-specific markers and receptors, the histocompatibility complex, cytokines/receptors, chemokines/receptors, adhesion molecules, components of the complement cascade, and signal transduction-related molecules. Interestingly, matrix metalloproteinases (MMPs) such as MMP-3 and MMP-9 were up-regulated, as further revealed by the reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. This indicates that MMPs may act as major regulators of the cytokine profile. Together, these findings provide new insight into the molecular events associated with the mechanism of the autoimmune genesis of myocarditis.

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