Abstract:
:Loss-of-function mutations in the Autoimmune Regulator (AIRE) gene cause a rare inherited form of autoimmune disease, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, also known as autoimmune polyglandular syndrome type 1. The patients suffer from multiple endocrine deficiencies, the most common manifestations being hypoparathyroidism, Addison's disease, hypogonadism, and secondary amenorrhea, usually accompanied by typical autoantibodies against the target tissues. Chronic mucocutaneous candidiasis is also a prominent part of the disease. The highest expression of AIRE is found in medullary thymic epithelial cells (mTECs). Murine studies suggest that it promotes ectopic transcription of self antigens in mTECs and is thus important for negative selection. However, failed negative selection alone is not enough to explain key findings in human patients, necessitating the search for alternative or additional pathogenetic mechanisms. A striking feature of the human AIRE-deficient phenotype is that all patients develop high titers of neutralizing autoantibodies against type I interferons, which have been shown to downregulate the expression of interferon-controlled genes. These autoantibodies often precede clinical symptoms and other autoantibodies, suggesting that they are a reflection of the pathogenetic process. Other cytokines are targeted as well, notably those produced by Th17 cells; these autoantibodies have been linked to the defect in anti-candida defenses. A defect in regulatory T cells has also been reported in several studies and seems to affect already the recent thymic emigrant population. Taken together, these findings in human patients point to a widespread disruption of T cell development and regulation, which is likely to have its origins in an abnormal thymic milieu. The absence of functional AIRE in peripheral lymphoid tissues may also contribute to the pathogenesis of the disease.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Arstila TP,Jarva Hdoi
10.3389/fimmu.2013.00313subject
Has Abstractpub_date
2013-10-07 00:00:00pages
313issn
1664-3224journal_volume
4pub_type
杂志文章,评审abstract::Heterogeneous populations of myeloid regulatory cells (MRC), including monocytes, macrophages, dendritic cells, and neutrophils, are found in cancer and infectious diseases. The inflammatory environment in solid tumors as well as infectious foci with persistent pathogens promotes the development and recruitment of MRC...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.01895
更新日期:2018-01-04 00:00:00
abstract::Neuroblastoma (NB) is the most common extracranial solid tumor in children and, in the high-risk group, has a 5-year mortality rate of ~50%. The high mortality rate and significant treatment-related morbidities associated with current standard of care therapies belie the critical need for more tolerable and effective ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00873
更新日期:2020-05-08 00:00:00
abstract::Bruton's tyrosine kinase (Btk) is a signaling molecule involved in development and activation of B cells through B-cell receptor (BCR) and Toll-like receptor (TLR) signaling. We have previously shown that transgenic mice that overexpress human Btk under the control of the CD19 promoter (CD19-hBtk) display spontaneous ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00095
更新日期:2019-01-30 00:00:00
abstract::Regulatory T cells (Tregs) are considered key players in the prevention of allograft rejection in transplanted patients. Belatacept (BLT) is an effective alternative to calcineurin inhibitors that appears to preserve graft survival and function; however, the impact of this drug in the homeostasis of Tregs in transplan...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00219
更新日期:2017-03-03 00:00:00
abstract::Mesenchymal stem cells (MSC) are under investigation as a therapy for a variety of disorders. Although animal models show long term regenerative and immunomodulatory effects of MSC, the fate of MSC after infusion remains to be elucidated. In the present study the localization and viability of MSC was examined by isola...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00297
更新日期:2012-09-26 00:00:00
abstract::The Autism Spectrum Disorder (ASD) is a heterogeneous group of neurodevelopmental disorders, only clinically diagnosed since the lack of reliable biomarkers. Autism etiology is probably attributable to the combination of genetic vulnerability and environmental factors, and recently, maternal immune activation has been...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02244
更新日期:2019-09-26 00:00:00
abstract::Mast cells (MCs) are considered as key effector cells in the elicitation of allergic symptoms, and they are essential players in innate and adaptive immune responses. In mice, two main types of MCs have been described: connective tissue MCs (CTMCs) and mucosal MCs (MMCs). However, little is known about the biological ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02399
更新日期:2019-10-15 00:00:00
abstract::CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells are essential to the balance between pro- and anti-inflammatory responses. There are two major subsets of Treg cells, "natural" Treg (nTreg) cells that develop in the thymus, and "induced" Treg (iTreg) cells that arise in the periphery from CD4(+) Foxp3(-) conventional...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00152
更新日期:2013-06-19 00:00:00
abstract::Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infe...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01083
更新日期:2017-09-11 00:00:00
abstract::Scleroderma (SSc) is an autoimmune connective tissue disease characterized by immune dysregulation, vasculopathy, and fibrosis. We have previously demonstrated that low Fli1 expression in SSc fibroblasts and endothelial cells plays an important role in SSc pathogenesis. Cells of myeloid and lymphoid origin also expres...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00800
更新日期:2020-05-19 00:00:00
abstract::Bullous pemphigoid (BP) is a common autoimmune blistering disease in which autoantibodies target the hemidesmosomal components BP180 and/or BP230 in basal keratinocytes. In BP, 80 to 90% of autoantibodies target the juxtamembranous extracellular non-collagenous 16th A (NC16A) domain of BP180. Recently, the administrat...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01224
更新日期:2019-05-29 00:00:00
abstract::Susceptibility to ankylosing spondylitis (AS) is polygenic with more than 100 genes identified to date. These include HLA-B27 and the aminopeptidases (ERAP1, ERAP2, and LNPEPS), which are involved in antigen processing and presentation to T-cells, and several genes (IL23R, IL6R, STAT3, JAK2, IL1R1/2, IL12B, and IL7R) ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.03132
更新日期:2019-01-10 00:00:00
abstract::Interleukin (IL)-2 is expressed during T cell activation and induces the proliferation and differentiation of T cells. CD4+Foxp3+ regulatory T cells (Tregs) constitutively express the high affinity IL-2 receptor (CD25/IL-2Rα) and rapidly respond to IL-2 to elaborate numerous suppressive mechanisms that limit immune-me...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00459
更新日期:2019-03-14 00:00:00
abstract::Vaccines aiming to promote T-cell-mediated immune responses have so far showed limited efficacy, and there is a need for novel strategies. Studies indicate that autophagy plays an inherent role in antigen processing and presentation for CD4(+) and CD8(+) T cells. Here, we report a novel vaccine strategy based on fusio...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2016.00167
更新日期:2016-05-10 00:00:00
abstract::Plasma cells (PCs), the B lineage cells responsible for producing and secreting antibodies (Abs), are critical cellular components of the humoral immune system. While most of the antibody-secreting cells in the body have a rather short lifetime of a few days, some of them can become long-lived and persist in the body ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00788
更新日期:2019-04-24 00:00:00
abstract::In primary systemic small vessel vasculitis autoantibodies are common and seem to play an important role in the pathogenesis. Autoantibodies in vasculitis are preferentially directed against components of the immune system or directly against components of the vessel wall. Plasmapheresis is often applied in emergency ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.02165
更新日期:2019-09-20 00:00:00
abstract::Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with immunomodulatory function. To study the mechanism by which MDSC affect antimicrobial immunity, we infected mice with two M. avium strains of differential virulence, highly virulent Mycobacterium avium subsp. avium strain 25291 (MAA) and low virule...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02317
更新日期:2018-10-16 00:00:00
abstract::The suppressor of cytokine signaling (SOCS) family of intracellular checkpoint inhibitors has received little recognition compared to other checkpoint inhibitors. Two members of this family, SOCS1 and SOCS3, are indispensable, since SOCS1 knockout in mice results in neonatal death due to interferon gamma (IFNγ) induce...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.582102
更新日期:2020-10-23 00:00:00
abstract::Hematopoietic stem cell transplantation from a haploidentical donor is increasingly used and has become a standard donor option for patients lacking an appropriately matched sibling or unrelated donor. Historically, prohibitive immunological barriers resulting from the high degree of HLA-mismatch included graft-vs.-ho...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00191
更新日期:2020-02-14 00:00:00
abstract::Objectives: Considering the critical role of microRNAs (miRNAs) in regulation of cell activation, we investigated their role in circulating type-2 conventional dendritic cells (cDC2s) of patients with primary Sjögren's syndrome (pSS) compared to healthy controls (HC). Methods: CD1c-expressing cDC2s were isolated from ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01335
更新日期:2019-06-20 00:00:00
abstract::T-cell memory to pathogens can be envisioned as a receptor-based imprint of the pathogenic environment on the naïve repertoire of clonotypes. Recurrent exposures to a pathogen inform and reinforce memory, leading to a mature state. The complexity and temporal stability of this system in man is only beginning to be ade...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01717
更新日期:2019-08-06 00:00:00
abstract::HERV-H endogenous retroviruses are thought to be essential to stem cell identity in humans. We embrace several decades of HERV-H research in order to relate the transcription of HERV-H loci to their genomic structure. We find that highly transcribed HERV-H loci are younger, more fragmented, and less likely to be prese...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01339
更新日期:2019-07-09 00:00:00
abstract::T cells play a critical role in cancer control, but a range of potent immunosuppressive mechanisms can be upregulated in the tumor microenvironment (TME) to abrogate their activity. While various immunotherapies (IMTs) aiming at re-invigorating the T-cell-mediated anti-tumor response, such as immune checkpoint blockad...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00925
更新日期:2019-06-06 00:00:00
abstract::Re-directing T cells via chimeric antigen receptors (CARs) was first tested in HIV-infected individuals with limited success, but these pioneering studies laid the groundwork for the clinically successful CD19 CARs that were recently FDA approved. Now there is great interest in revisiting the concept of using CAR-expr...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.02310
更新日期:2019-09-27 00:00:00
abstract::Treatment with the macrolide antibiotic azithromycin (AZM) is an important intervention for controlling infection of children with Bordetella pertussis and as a prophylaxis for preventing transmission to family members. However, antibiotics are known to have immunomodulatory effects independent of their antimicrobial ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01764
更新日期:2018-07-30 00:00:00
abstract::Functional impairment of T-cells and a concomitant augmented expression of programmed death-1 (PD-1) have been observed in visceral leishmaniasis patients, as well as in experimental models for visceral and cutaneous leishmaniasis. The PD-1/PD-1-ligand (PD-1/PD-L) interaction negatively regulates T-cell effector funct...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01880
更新日期:2017-12-22 00:00:00
abstract::The pathogenicity of group A Streptococcus (GAS) is mediated by direct bacterial invasivity and toxin-associated damage. Among the extracellular products, the exotoxin streptolysin O (SLO) is produced by almost all GAS strains. SLO is a pore forming toxin (PFT) hemolitically active and extremely toxic in vivo. Recent ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.507092
更新日期:2020-12-08 00:00:00
abstract::Regulatory T-cells (Tregs) mediate their suppressive action by acting directly on conventional T-cells (Tcons) or dendritic cells (DCs). One mechanism of Treg suppression is the increase of cyclic adenosine 3',5'-monophosphate (cAMP) levels in target cells. Tregs utilize cAMP to control Tcon responses, such as prolife...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00216
更新日期:2016-06-02 00:00:00
abstract::Construction of an optimal vaccine against tumors relies on the availability of appropriate tumor-specific antigens capable to stimulate CD4+ T helper cells (TH) and CD8+ cytolytic T cells (CTL). CTL are considered the major effectors of the anti-tumor adaptive immune response as they recognize antigens presented on M...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.01806
更新日期:2019-07-30 00:00:00
abstract::There have been few in vivo studies on the effect of aluminum hydroxide adjuvant and its influence on the immune response to vaccination. In this study, lambs received a parallel subcutaneous treatment with either commercial vaccines containing aluminum hydroxide or an equivalent dose of this compound only with the ai...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02406
更新日期:2018-10-23 00:00:00