scholarly journals Intrinsic and damage-induced JAK/STAT signaling regulate developmental timing by the Drosophila prothoracic gland

2021 ◽  
Author(s):  
Xueya Cao ◽  
Marta Rojas ◽  
José Carlos Pastor-Pareja
Keyword(s):  
Transcription Factor ◽  
Immune Responses ◽  
Resource Availability ◽  
Tissue Damage ◽  
Normal Development ◽  
Prothoracic Gland ◽  
Multiple Organs ◽  
Stat Signaling ◽  
Developmental Role ◽  
Major Mediator

Development involves tightly paced, reproducible sequences of events, yet it must adjust to conditions external to it, such as resource availability and organismal damage. A major mediator of damage-induced immune responses in vertebrates and insects is JAK/STAT signaling. At the same time, JAK/STAT activation by the Drosophila Upd cytokines is pleiotropically involved in normal development of multiple organs. Whether inflammatory and developmental roles of JAK/STAT intersect is unknown. Here, we show that JAK/STAT is active during development of the prothoracic gland (PG), the organ that controls metamorphosis onset through ecdysone production. Reducing JAK/STAT signaling decreased PG size and slightly advanced metamorphosis. Conversely, JAK/STAT hyperactivation, achieved through overexpression of pathway components or SUMOylation loss, caused PG hypertrophy and metamorphosis delay. Interestingly, tissue damage and tumors, known to secrete Upd cytokines, also activated JAK/STAT in the PG and delayed metamorphosis. Finally, we show that expression of transcription factor Apontic, a JAK/STAT target in the PG, recapitulates PG hypertrophy and metamorphosis delay. JAK/STAT damage signaling, therefore, regulates metamorphosis onset at least in part by coopting its developmental role in the PG.

scholarly journals Intrinsic and tumor-induced JAK/STAT signaling regulate developmental timing by the Drosophila prothoracic gland

2021 ◽  
Author(s):  
Xueya Cao ◽  
Jose Carlos Pastor-Pareja
Keyword(s):  
Transcription Factor ◽  
Immune Responses ◽  
Resource Availability ◽  
Tissue Damage ◽  
Normal Development ◽  
Prothoracic Gland ◽  
Multiple Organs ◽  
Stat Signaling ◽  
Developmental Role ◽  
Major Mediator

Development involves tightly paced, reproducible sequences of events, yet it must adjust to conditions external to it, such as resource availability and organismal damage. A major mediator of damage-induced immune responses in vertebrates and insects is JAK/STAT signaling. At the same time, JAK/STAT activation by the Drosophila Upd cytokines is pleiotropically involved in normal development of multiple organs. Whether inflammatory and developmental roles of JAK/STAT intersect is unknown. Here, we show that JAK/STAT is active during development of the prothoracic gland (PG), the organ that controls metamorphosis onset through ecdysone production. Reducing JAK/STAT signaling decreased PG size and slightly advanced metamorphosis. Conversely, JAK/STAT hyperactivation, achieved through overexpression of pathway components or SUMOylation loss, caused PG hypertrophy and metamorphosis delay. Interestingly, tissue damage and tumors, known to secrete Upd cytokines, also activated JAK/STAT in the PG and delayed metamorphosis. Finally, we show that expression of transcription factor Apontic, a JAK/STAT target in the PG, recapitulates PG hypertrophy and metamorphosis delay. JAK/STAT damage signaling, therefore, regulates metamorphosis onset at least in part by coopting its developmental role in the PG.

Enhanced immune responses, PI3K/AKT and JAK/STAT signaling pathways following hepatitis C virus eradication by direct-acting antiviral therapy among Egyptian patients: a case control study

2021 ◽  
Author(s):  
Haidi Karam-Allah Ramadan ◽  
Gamal Badr ◽  
Nancy K Ramadan ◽  
Aml Sayed
Keyword(s):  
Immune Response ◽  
Liver Cirrhosis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Immune Responses ◽  
Signaling Pathways ◽  
Liver Diseases ◽  
Stat Signaling ◽  
Chronic Hcv ◽  
Direct Acting

Abstract The use of direct-acting antivirals (DAAs) therapy for the treatment of hepatitis C virus (HCV) results in a high sustained virological response (SVR) and subsequently alters liver immunologic environment. However, hepatocellular carcinoma (HCC) may occur after DAAs treatment. We aimed to clarify changes of immune responses, PI3K/AKT and JAK/STAT signaling pathways in HCV-induced liver diseases and HCC following DAAs treatment. Four cohorts are classified as chronic HCV patients, HCV-related cirrhosis without HCC, HCV-related cirrhosis and HCC, and healthy control group. The patient groups were further divided into treated or untreated with DAAs with SVR12. Increased percentages of CD3, CD8 and CD4, decreased CD4/FoxP3/CD25, CD8/PD-1 and CD19/PDL-1 were found in DAAs-treated patients in the three HCV groups. Following DAAs therapy, the levels of ROS, IL-1β, IL-6, IL-8 and TNF-α were significantly decreased in the three HCV groups. Treated HCV patients showed up regulation of p-AKT and p-STAT5 and down regulation of p-STAT3, HIF-1α and COX-2. In conclusion, DAAs enhance the immune response in chronic HCV and liver cirrhosis, hence our study is the first to show change in PI3K/AKT and JAK/STAT signaling pathways in different HCV-induced liver diseases after DAAs. In chronic HCV, DAAs have better impact on the immune response while in liver cirrhosis not all immune changes were prominent.

scholarly journals Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sandeep K. Gupta ◽  
Natalie A. Parlane ◽  
Dongwen Luo ◽  
Bernd H. A. Rehm ◽  
Axel Heiser ◽  
...  
Keyword(s):  
Immune Responses ◽  
Fusion Protein ◽  
Mycobacterium Avium ◽  
Low Cost ◽  
Multiple Organs ◽  
T Cell Immune Responses ◽  
Protein Particle ◽  
Mycobacterium Avium Subsp Paratuberculosis ◽  
Eventual Death ◽  
Fusion Antigen

AbstractMycobacterium avium subspecies paratuberculosis (MAP) causes chronic progressive granulomatous enteritis leading to diarrhoea, weight loss, and eventual death in ruminants. Commercially available vaccines provide only partial protection against MAP infection and can compromise the use of bovine tuberculosis diagnostic tests. Here, we report the development of a protein-particle-based vaccine containing MAP antigens Ag85A202–347-SOD1–72-Ag85B173–330-74F1–148+669–786 as a fusion (‘MAP fusion protein particle’). The fusion antigen displayed on protein particles was identified using mass spectrometry. Surface exposure and accessibility of the fusion antigen was confirmed by flow cytometry and ELISA. The MAP fusion protein particle vaccine induced strong antigen-specific T-cell immune responses in mice, as indicated by increased cytokine (IFN-γ and IL-17A) and costimulatory signals (CD40 and CD86) in these animals. Following MAP-challenge, a significant reduction in bacterial burden was observed in multiple organs of the mice vaccinated with the MAP fusion protein particle vaccine compared with the PBS group. The reduction in severity of MAP infection conferred by the MAP fusion protein particle vaccine was similar to that of Silirum and recombinant protein vaccines. Overall, the results provide evidence that MAP antigens can be engineered as a protein particulate vaccine capable of inducing immunity against MAP infection. This utility offers an attractive platform for production of low-cost particulate vaccines against other intracellular pathogens.

scholarly journals Involvement of RNA Polymerase III in Immune Responses

2015 ◽  
Vol 35 (10) ◽  
pp. 1848-1859 ◽  
Author(s):  
Damian Graczyk ◽  
Robert J. White ◽  
Kevin M. Ryan
Keyword(s):  
Transcription Factor ◽  
Immune Responses ◽  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Trna Genes ◽  
Malignant Cells ◽  
Polymerase Iii ◽  
Mouse Macrophages ◽  
Tightly Coupled ◽  
Pol Iii

Inflammation in the tumor microenvironment has many tumor-promoting effects. In particular, tumor-associated macrophages (TAMs) produce many cytokines which can support tumor growth by promoting survival of malignant cells, angiogenesis, and metastasis. Enhanced cytokine production by TAMs is tightly coupled with protein synthesis. In turn, translation of proteins depends on tRNAs, short abundant transcripts that are made by RNA polymerase III (Pol III). Here, we connect these facts by showing that stimulation of mouse macrophages with lipopolysaccharides (LPS) from the bacterial cell wall causes transcriptional upregulation of tRNA genes. The transcription factor NF-κB is a key transcription factor mediating inflammatory signals, and we report that LPS treatment causes an increased association of the NF-κB subunit p65 with tRNA genes. In addition, we show that p65 can directly associate with the Pol III transcription factor TFIIIB and that overexpression of p65 induces Pol III-dependent transcription. As a consequence of these effects, we show that inhibition of Pol III activity in macrophages restrains cytokine secretion and suppresses phagocytosis, two key functional characteristics of these cells. These findings therefore identify a radical new function for Pol III in the regulation of macrophage function which may be important for the immune responses associated with both normal and malignant cells.

scholarly journals Whole-Animal Chemical Screen Identifies Colistin as a New Immunomodulator That Targets Conserved Pathways

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Yun Cai ◽  
Xiou Cao ◽  
Alejandro Aballay
Keyword(s):  
Transcription Factor ◽  
Immune Responses ◽  
Immune Activation ◽  
Bacterial Infections ◽  
Mitogen Activated Protein Kinase ◽  
Resistant Bacteria ◽  
Long Term Outcome ◽  
Gram Negative ◽  
Content Type ◽  
Chemical Screen

ABSTRACTThe purpose of this study was to take advantage of the nematodeCaenorhabditis elegansto perform a whole-animal chemical screen to identify potential immune activators that may confer protection against bacterial infections. We identified 45 marketed drugs, out of 1,120 studied compounds, that are capable of activating a conserved p38/PMK-1 mitogen-activated protein kinase pathway required for innate immunity. One of these drugs, the last-resort antibiotic colistin, protected against infections by the Gram-negative pathogensYersinia pestisandPseudomonas aeruginosabut not by the Gram-positive pathogensEnterococcus faecalisandStaphylococcus aureus. Protection was independent of the antibacterial activity of colistin, since the drug was administered prophylactically prior to the infections and it was also effective against antibiotic-resistant bacteria. Immune activation by colistin is mediated not only by the p38/PMK-1 pathway but also by the conserved FOXO transcription factor DAF-16 and the transcription factor SKN-1. Furthermore, p38/PMK-1 was found to be required in the intestine for immune activation by colistin. Enhanced p38/PMK-1-mediated immune responses by colistin did not reduce the bacterial burden, indicating that the pathway plays a role in the development of host tolerance to infections by Gram-negative bacteria.IMPORTANCEThe innate immune system represents the front line of our defenses against invading microorganisms. Given the ever-increasing resistance to antibiotics developed by bacterial pathogens, the possibility of boosting immune defenses represents an interesting, complementary approach to conventional antibiotic treatments. Here we report that the antibiotic colistin can protect against infections by a mechanism that is independent of its microbicidal activity. Prophylactic treatment with colistin activates a conserved p38/PMK-1 pathway in the intestine that helps the host better tolerate a bacterial infection. Since p38/PMK-1-mediated immune responses appear to be conserved from plants to mammals, colistin may also activate immunity in higher organisms, including humans. Antibiotics with immunomodulatory properties have the potential of improving the long-term outcome of patients with chronic infectious diseases.

Retinoic acid establishes ventral retinal characteristics

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 195-204 ◽  
Author(s):  
G.A. Hyatt ◽  
E.A. Schmitt ◽  
N. Marsh-Armstrong ◽  
P. McCaffery ◽  
U.C. Drager ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Retinoic Acid ◽  
Optic Nerve ◽  
Normal Development ◽  
Cell Content ◽  
Optic Stalk ◽  
Eye Field ◽  
Dorsal Retina ◽  
Choroid Fissure

The developing eye is known to be rich in retinoic acid (RA), and perturbations in RA levels during formation of the optic primordia, as well as RA receptor mutations, cause retinal malformations, especially in ventral eye regions. To test the hypothesis that RA plays a role in the establishment of ventral retinal characteristics, we examined several dorsal and ventral ocular markers in RA-treated zebrafish. The optic stalk represents the ventral-most region of the early eye field. During normal development, the optic stalks constrict, decreasing in width and are gradually replaced by the optic nerve. Systemic high RA levels cause an expansion in the optic stalk with an increased cell content and a patent lumen. In addition, the stalks do not constrict and persist into later stages of development indicating an enhancement of early ventral eye characteristics. Expression of the transcription factor pax[b], normally confined to the ventral retina, expands into the dorsal retina following RA treatment, whereas msh[c], normally expressed in the dorsal retinal pole, disappears. Activity of an aldehyde dehydrogenase that normally occupies the dorsal third of the retina is reduced or abolished following high systemic RA. When a localized RA source, an RA-soaked bead, is placed next to the developing eye, a fissure resembling the choroid fissure appears in the eye facing the bead. Taken together, these observations suggest that RA is involved in the determination of the ventral retina.

scholarly journals NFAT control of immune function: New Frontiers for an Abiding Trooper

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 260 ◽  
Author(s):  
Martin Vaeth ◽  
Stefan Feske
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Immune Responses ◽  
Physiological Function ◽  
Large Body ◽  
Immunological Tolerance ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Humoral Immune ◽  
Humoral Immune Responses

Nuclear factor of activated T cells (NFAT) was first described almost three decades ago as a Ca2+/calcineurin-regulated transcription factor in T cells. Since then, a large body of research uncovered the regulation and physiological function of different NFAT homologues in the immune system and many other tissues. In this review, we will discuss novel roles of NFAT in T cells, focusing mainly on its function in humoral immune responses, immunological tolerance, and the regulation of immune metabolism.

scholarly journals CD4 T Helper Cell Subsets and Related Human Immunological Disorders

2020 ◽  
Vol 21 (21) ◽  
pp. 8011 ◽  
Author(s):  
Xiaoliang Zhu ◽  
Jinfang Zhu
Keyword(s):  
Transcription Factor ◽  
Immune System ◽  
Immune Responses ◽  
Critical Role ◽  
Cell Subset ◽  
Lymphoid Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
Th2 Cells ◽  
T Helper

The immune system plays a critical role in protecting hosts from the invasion of organisms. CD4 T cells, as a key component of the immune system, are central in orchestrating adaptive immune responses. After decades of investigation, five major CD4 T helper cell (Th) subsets have been identified: Th1, Th2, Th17, Treg (T regulatory), and Tfh (follicular T helper) cells. Th1 cells, defined by the expression of lineage cytokine interferon (IFN)-γ and the master transcription factor T-bet, participate in type 1 immune responses to intracellular pathogens such as mycobacterial species and viruses; Th2 cells, defined by the expression of lineage cytokines interleukin (IL)-4/IL-5/IL-13 and the master transcription factor GAΤA3, participate in type 2 immune responses to larger extracellular pathogens such as helminths; Th17 cells, defined by the expression of lineage cytokines IL-17/IL-22 and the master transcription factor RORγt, participate in type 3 immune responses to extracellular pathogens including some bacteria and fungi; Tfh cells, by producing IL-21 and expressing Bcl6, help B cells produce corresponding antibodies; whereas Foxp3-expressing Treg cells, unlike Th1/Th2/Th17/Tfh exerting their effector functions, regulate immune responses to maintain immune cell homeostasis and prevent immunopathology. Interestingly, innate lymphoid cells (ILCs) have been found to mimic the functions of three major effector CD4 T helper subsets (Th1, Th2, and Th17) and thus can also be divided into three major subsets: ILC1s, ILC2s, and ILC3s. In this review, we will discuss the differentiation and functions of each CD4 T helper cell subset in the context of ILCs and human diseases associated with the dysregulation of these lymphocyte subsets particularly caused by monogenic mutations.

scholarly journals Dynamic Competition of Polycomb and Trithorax in Transcriptional Programming

2020 ◽  
Vol 89 (1) ◽  
pp. 235-253 ◽  
Author(s):  
Mitzi I. Kuroda ◽  
Hyuckjoon Kang ◽  
Sandip De ◽  
Judith A. Kassis
Keyword(s):  
Transcription Factor ◽  
Histone Modifications ◽  
Dna Sequences ◽  
Normal Development ◽  
Polycomb Group ◽  
Cell Type ◽  
Trithorax Group ◽  
Cell Type Specific ◽  
Chromatin Proteins ◽  
Regulatory Potential

Predicting regulatory potential from primary DNA sequences or transcription factor binding patterns is not possible. However, the annotation of the genome by chromatin proteins, histone modifications, and differential compaction is largely sufficient to reveal the locations of genes and their differential activity states. The Polycomb Group (PcG) and Trithorax Group (TrxG) proteins are the central players in this cell type–specific chromatin organization. PcG function was originally viewed as being solely repressive and irreversible, as observed at the homeotic loci in flies and mammals. However, it is now clear that modular and reversible PcG function is essential at most developmental genes. Focusing mainly on recent advances, we review evidence for how PcG and TrxG patterns change dynamically during cell type transitions. The ability to implement cell type–specific transcriptional programming with exquisite fidelity is essential for normal development.

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