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Recent Developments in Therapies and Strategies Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Misbah Hameed, M. Zia-Ul-Haq, Marius Moga
Interferons are the signaling proteins that are released in the body in response to the viral infections. IFN-I is a cytokine that is released after viral infection. It is immediately recognized as IFNAR receptors are present on the plasma membrane of most cells. Where it induces signal transducer and activator of transcription 1 (STAT1) phosphorylation. STAT1 in return activate ISG, which interfere with viral replication, spreading, and activating the adaptive immune response. ISGs has several pattern recognition receptors (PRRs) for recognition of infectious agents. The ISGs has role in decreasing membrane fluidity, reducing the membrane fusion and the escape of the virus. ISGs also can prevent viral cycle at several steps because of some antiviral proteins [65].
Immunology (primary Immunodeficiency Syndromes
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Stephan Strobel, Alison M. Jones
All patients have extremely high IgE levels, varying with age at presentation. Under 1 year IgE may be >1000 IU/ml, but in older patients may be 10,000– 20,000 IU/ml or higher. Patients with severe atopic disease alone may also have very high IgE levels but usually do not exhibit other clinical features of HIES. Other immunology investigations are usually normal, although defects in neutrophil function have been described. The diagnosis is confirmed by demonstration of a mutation in Stat-3.
Overview of JAK-STAT Pathways in Spondyloarthritis
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Smriti K. Raychaudhuri, Sanchita Raychaudhuri, Debasis Bagchi, Anand Swaroop, Siba P. Raychaudhuri
JAK1 and JAK2 have been demonstrated to play an important role in Th1 and Th17 cell differentiation, while STAT1 is critical to T-lymphocyte differentiation. STAT1 is activated by type I IFNs and IFN-γ and plays an important role in immune responses. IRF1 is the first member identified in the interferon-regulatory factor (IRF) family and is involved in innate and adaptive immune responses. Impaired or absent Th1-type immune responses favor Th2 differentiation in IRF1-deficient mice. NOS2-derived nitric oxide (NO), a key factor in immunoregulation, can inhibit Th1 as well as Th2 cytokine production and regulate the development of FoxP3+ Treg cells. JAK-STAT signaling pathway genes, including JAK1, JAK2, STAT1, IRF1, and NOS2, are strongly linked to T cells and may be involved in the pathophysiology of acute anterior uveitis (AAU), AS, psoriasis, and psoriatic arthritis (PsA).
JAK inhibitors in dermatology: the road travelled and path ahead, a narrative review
Published in Expert Review of Clinical Pharmacology, 2023
Aishwarya Muddebihal, Ananta Khurana, Kabir Sardana
Vitiligo is an acquired depigmenting disorder due to autoimmune destruction of melanocytes of hair/skin or both affecting 0.5–2% of population globally [64]. The pathophysiology is multifactorial and INF- γ secreting CD8 + T cells play a central role. IFN-γ, a type II interferon, activates the JAK/STAT pathway by binding to a IFNGR1 and IFNGR2 cell surface receptors which are related to JAK1 and JAK2 respectively. This leads to the phosphorylation of STAT1, which initiates gene transcription. Thus, blocking INF-γ signaling mediated via JAK/STAT pathway has a therapeutic role in the disease [65]. IL-15, another prominent cytokine involved in the pathogenesis of vitiligo, signals via JAK1 & JAK 3 resulting in STAT 5 activation. In the setting of oxidative stress damage to keratinocytes and relapse IL-15 and IL-15 Rα activate the resident CD8 + T memory cells and cause melanocyte destruction [66]. Studies have shown higher serum levels of IL-15 in vitiligo patients compared to control group and further, a positive correlation was also observed with disease extent [67].
IFN-γ-induced ER stress impairs autophagy and triggers apoptosis in lung cancer cells
Published in OncoImmunology, 2021
Can Fang, Tao Weng, Shaojie Hu, Zhiwei Yuan, Hui Xiong, Bing Huang, Yixin Cai, Lequn Li, Xiangning Fu
IFN-γ engaging with its receptor leads to the recruitment and activation of JAK1 and JAK2, which results in the activation of STAT1, a pivotal transcription factor. STAT1 regulates the expression of a wide range of immune-related genes.8 IFN-γ signaling can also activate the MAPK, PI3K-AKT-mTOR, and NF-κB signaling pathways to regulate gene transcription and promote mRNA translation.9–11 Recently, Yu et al. have shown that IFN-γ promotes yes-associated protein (YAP) condensation in tumor cells after anti-PD-1 therapy. The YAP condensation creates a transcription hub that increases the expression of immunosuppressive target genes, independent of the canonical STAT1-IRF1 transcription program.12 Increased protein synthesis demands may disrupt endoplasmic reticulum (ER) homeostasis, leading to a condition referred to as ER stress.13 Whether IFN-γ induces ER stress in lung adenocarcinoma cells is yet to be determined.
Identification of key biomolecules in rheumatoid arthritis through the reconstruction of comprehensive disease-specific biological networks
Published in Autoimmunity, 2020
PPI network was constructed around proteins encoded by core 25 DEGs via their physical interactions obtained from the previous study. For core DEGs, the first neighbour enriched PPI network was constructed including 201 nodes and 210 edges (Figure 3). In topological analyses of the PPI network, degree (local-based) and betweenness centrality (global-based) metrics [6] were used to identify the highly connected proteins, i.e. hub proteins (Table 3), which might take a crucial role in disease pathogenesis. Signal Transducer and Activator of Transcription 1 (STAT1), Rac Family Small GTPase 2 (RAC2) and Kynureninase (KYNU) as hub proteins were determined. Hub proteins were investigated in the GeneCards database [49]. STAT1 is STAT family members are phosphorylated by the receptor-associated kinases and it comes into prominence of response to cytokines and growth factor. RAC2 is a plasma membrane-associated small GTPase that regulates a wide variety of processes in the cell, including secretory processes, differentiation, movement and epithelial cell polarisation. KYNU is involved in the biosynthesis of NAD cofactors from tryptophan through the kynurenine pathway.