Update on Aire and thymic negative selection Passos, Geraldo A.; Speck‐Hernandez, Cesar A.; Assis, Amanda F. ...
Immunology,
January 2018, Letnik:
153, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Summary
Twenty years ago, the autoimmune regulator (Aire) gene was associated with autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy, and was cloned and sequenced. Its importance goes ...beyond its link with human autoimmune disease. Aire identification opened new perspectives to better understand the molecular basis of central tolerance and self–non‐self distinction, the main properties of the immune system. Since 1997, a growing number of immunologists and molecular geneticists have made important discoveries about the function of Aire, which is essentially a pleiotropic gene. Aire is one of the functional markers in medullary thymic epithelial cells (mTECs), controlling their differentiation and expression of peripheral tissue antigens (PTAs), mTEC–thymocyte adhesion and the expression of microRNAs, among other functions. With Aire, the immunological tolerance became even more apparent from the molecular genetics point of view. Currently, mTECs represent the most unusual cells because they express almost the entire functional genome but still maintain their identity. Due to the enormous diversity of PTAs, this uncommon gene expression pattern was termed promiscuous gene expression, the interpretation of which is essentially immunological – i.e. it is related to self‐representation in the thymus. Therefore, this knowledge is strongly linked to the negative selection of autoreactive thymocytes. In this update, we focus on the most relevant results of Aire as a transcriptional and post‐transcriptional controller of PTAs in mTECs, its mechanism of action, and its influence on the negative selection of autoreactive thymocytes as the bases of the induction of central tolerance and prevention of autoimmune diseases.
Aire gene identification opened new perspectives to better understand the molecular basis of central tolerance and self–non‐self distinction.
Aire is one of the functional markers in medullary thymic epithelial cells (mTECs), controlling their differentiation and expression of peripheral tissue antigens, mTEC–thymocyte adhesion and the expression of microRNAs, among other functions.
Currently, mTECs represent the most unusual cells because they express almost the entire functional genome but still maintain their identity.”
The development of new strategies to control pest insects is required, in combination with conventional pesticides or replacing them. Essential oils produced from botanical extracts used in ...management programs should be effective against pests and selective to natural enemies.
Tuta absoluta
(Meyrick) (Lepidoptera: Gelechiidae) is one of the most destructive pests of solanaceous crops in the world, and a possible management strategy consists of releases of the predator
Nesidiocoris tenuis
(Hemiptera: Miridae), along with botanical applications. The objective of this study was to evaluate the effects of Prev-am
®
oil on
T. absoluta
offspring, either with or without the predator
N. tenuis
, as well as the oil’s effects on
N. tenuis
predatory behavior and longevity. The oil’s effects were compared with distilled water (control) and a synthetic pesticide (lambda-cyhalothrin). The response of populations to lambda-cyhalothrin was similar to that with Prev-am
®
, compared to the control, showing that
N. tenuis
had higher capacity to reduce
T. absoluta
populations. The survival analysis of predators exposed to Prev-am
®
indicates that none of the concentrations differed significantly from the control. In addition, the canonical variate analysis indicated significant overall differences in the predator behavior submitted to different treatments, suggesting that synthetic pesticide treatment affected predator behavior when compared to control and Prev-am
®
. Reduction in predatory voracity of
N. tenuis
adults exposed to leaves treated with pesticide and biopesticide was significant compared to the control treatment. The results obtained could improve IPM programs against
T. absoluta
through the Prev-am
®
applications and
N. tenuis
releases.
Regardless the regulatory function of microRNAs (miRNA), their differential expression pattern has been used to define miRNA signatures and to disclose disease biomarkers. To address the question of ...whether patients presenting the different types of diabetes mellitus could be distinguished on the basis of their miRNA and mRNA expression profiling, we obtained peripheral blood mononuclear cell (PBMC) RNAs from 7 type 1 (T1D), 7 type 2 (T2D), and 6 gestational diabetes (GDM) patients, which were hybridized to Agilent miRNA and mRNA microarrays. Data quantification and quality control were obtained using the Feature Extraction software, and data distribution was normalized using quantile function implemented in the Aroma light package. Differentially expressed miRNAs/mRNAs were identified using Rank products, comparing T1DxGDM, T2DxGDM and T1DxT2D. Hierarchical clustering was performed using the average linkage criterion with Pearson uncentered distance as metrics.
The use of the same microarrays platform permitted the identification of sets of shared or specific miRNAs/mRNA interaction for each type of diabetes. Nine miRNAs (hsa-miR-126, hsa-miR-1307, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144, hsa-miR-199a-5p, hsa-miR-27a, hsa-miR-29b, and hsa-miR-342-3p) were shared among T1D, T2D and GDM, and additional specific miRNAs were identified for T1D (20 miRNAs), T2D (14) and GDM (19) patients. ROC curves allowed the identification of specific and relevant (greater AUC values) miRNAs for each type of diabetes, including: i) hsa-miR-1274a, hsa-miR-1274b and hsa-let-7f for T1D; ii) hsa-miR-222, hsa-miR-30e and hsa-miR-140-3p for T2D, and iii) hsa-miR-181a and hsa-miR-1268 for GDM. Many of these miRNAs targeted mRNAs associated with diabetes pathogenesis.
These results indicate that PBMC can be used as reporter cells to characterize the miRNA expression profiling disclosed by the different diabetes mellitus manifestations. Shared miRNAs may characterize diabetes as a metabolic and inflammatory disorder, whereas specific miRNAs may represent biological markers for each type of diabetes, deserving further attention.
Zoophytophagous hemipteran predators provide relevant biological control services and their applications are consolidated in greenhouse pest management. The use of plant essential oils (EOs) for ...sustainable crop protection is being currently promoted. However, further knowledge of the potential side effects of EOs on predatory mirids (Hemiptera: Miridae) is required. Here, we evaluated the non-target impact of four EOs (anise, fennel, garlic and lavender) on the generalist predator
Nesidiocoris tenuis
(Reuter) in the laboratory. The baseline toxicity of EOs was firstly assessed on
N. tenuis
adults following topical contact exposure. Then, the predator reproduction and orientation behavior was tested following the exposure to three estimated EO lethal concentrations (LC
1
, LC
10
and LC
30
). Garlic EO had the lowest estimated LCs (e.g., LC
30
1.34 mg mL
−1
), being thus the most toxic compound among the tested EOs. The estimated LC
30
s for lavender, anise and fennel EOs were 2.75, 4.55 and 5.17 mg mL
−1
, respectively. The fertility and the orientation behavior of
N. tenuis
females was negatively affected by all the EOs at the highest tested concentration. Nevertheless, anise EO at LC
1
and LC
10
caused no sublethal effects on
N. tenuis
. Our findings suggest that careful attention should be given when EOs are used in combination with
N. tenuis
in pest management programs.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint destruction and severe morbidity. Cigarette smoking (CS) can exacerbate the incidence and severity of RA. Although ...Th17 cells and the Aryl hydrocarbon receptor (AhR) have been implicated, the mechanism by which CS induces RA development remains unclear. Here, using transcriptomic analysis, we show that
is specifically induced in Th17 cells in the presence of either AhR agonist or CS-enriched medium.
thus induced is packaged into extracellular vesicles produced by Th17 and acts as a proinflammatory mediator increasing osteoclastogenesis through the down-regulation of COX2. In vivo, articular knockdown of
in murine arthritis models reduces the number of osteoclasts in the joints. Clinically, RA patients express higher levels of
than do healthy individuals. This increase is further elevated by cigarette smoking. Together, these results reveal a hitherto unrecognized mechanism by which CS could exacerbate RA and further advance understanding of the impact of environmental factors on the pathogenesis of chronic inflammatory diseases.
In autoimmune type 1 diabetes mellitus (T1D), auto-reactive clones of CD4+ and CD8+ T lymphocytes in the periphery evolve into pancreas-infiltrating T lymphocytes (PILs), which destroy ...insulin-producing beta-cells through inflammatory insulitis. Previously, we demonstrated that, during the development of T1D in non-obese diabetic (NOD) mice, a set of immune/inflammatory reactivity genes were differentially expressed in T lymphocytes. However, the posttranscriptional control involving miRNA interactions that occur during the evolution of thymocytes into PILs remains unknown. In this study, we postulated that miRNAs are differentially expressed during this period and that these miRNAs can interact with mRNAs involved in auto-reactivity during the progression of insulitis. To test this hypothesis, we used NOD mice to perform, for the first time, a comprehensive survey of miRNA and mRNA expression as thymocytes mature into peripheral CD3+ T lymphocytes and, subsequently, into PILs. Reconstruction of miRNA-mRNA interaction networks for target prediction revealed the participation of a large set of miRNAs that regulate mRNA targets related to apoptosis, cell adhesion, cellular regulation, cellular component organization, cellular processes, development and the immune system, among others. The interactions between miR-202-3p and the Ccr7 chemokine receptor mRNA or Cd247 (Cd3 zeta chain) mRNA found in PILs are highlighted because these interactions can contribute to a better understanding of how the lack of immune homeostasis and the emergence of autoimmunity (e.g., T1D) can be associated with the decreased activity of Ccr7 or Cd247, as previously observed in NOD mice. We demonstrate that these mRNAs are controlled at the posttranscriptional level in PILs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Macrolophus basicornis
(Stal) (Hemiptera: Miridae) is a promising biological control agent against tomato pests, mainly the South American tomato pinworm
Tuta absoluta
(Meyrick) (Lepidoptera: ...Gelechiidae). Nevertheless, the amount of pesticides used in tomato crops could compromise the effectiveness of
M. basicornis
in pest control. Thus, the present research aims to evaluate the lethal and sublethal effects of five insecticides (spinetoram, chlorantraniliprole + abamectin, triflumuron, tebufenozide, and abamectin) commonly used in tomato crops on
M. basicornis
. Third instar nymphs were exposed to dry residues of insecticides on tomato seedlings, and adults were directly sprayed using a Potter precision tower. Abamectin caused the highest mortality rate (79.98%) of
M. basicornis
nymphs. Females exposed to spinetoram during the nymphal stage showed a reduction in tibia length. Except for spinetoram, all other insecticides significantly influenced adult longevity. All insecticide treatments caused a reduction in female offspring. However, the growth of males and females (
F
1
generation) issued from adults treated did not differ significantly from the control. In the predator flight bioassay, males in the first evaluation showed a reduction in flight activity following exposure to chlorantraniliprole + abamectin and to tebufenozide. Overall, all insecticides tested caused negative effects on
M. basicornis
.
PDF
