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Topic Review
Inflammatory Bowel Disease Treatments
Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with a highly heterogeneous presentation. It has a relapsing and remitting clinical course that necessitates lifelong monitoring and treatment. Although the availability of a variety of effective therapeutic options including immunomodulators and biologics (such as TNF, CAM inhibitors) has led to a paradigm shift in the treatment outcomes and clinical management of IBD patients, some patients still either fail to respond or lose their responsiveness to therapy over time.
  • 941
  • 05 Jul 2022
Topic Review
Rheumatic Manifestations for ICIs
Immune checkpoint inhibitors (ICI) are monoclonal antibodies that activate the immune system aiming at enhancing antitumor immunity.  Their clinical efficacy is well documented but the side effects associated with their use are still under investigation.  These drugs cause several immune related adverse events (ir-AE) some of which stand within the field of Rheumatology.  Herein, we performed a literature review in an effort to evaluate all publicly available clinical data regarding rheumatic manifestations associated with ICI.  The most common musculoskeletal ir-AEs are inflammatory arthritis, polymyalgia rheumatica and myositis.  Non musculoskeletal rheumatic manifestations are less frequent with the most prominent being sicca, vasculitides and sarcoidosis.  Cases of systemic lupus erythematosus or scleroderma are extremely rare.  The majority of musculoskeletal ir-AE are of mild/moderate severity and can be managed with steroids with no need for ICI discontinuation.  In severe cases, more intense immunosuppressive therapy and permanent ICI discontinuation may be employed.  Oncologists should periodically screen patients receiving ICI for new onset inflammatory musculoskeletal complaints and seek a rheumatology consultation in cases of persisting symptoms.
  • 939
  • 28 Oct 2020
Topic Review
Immunoglobulins with Non-Canonical Functions
Immunoglobulins are known to combine various effector mechanisms of the adaptive and the innate immune system. Classical immunoglobulin functions are associated with antigen recognition and the initiation of innate immune responses. However, in addition to classical functions, antibodies exhibit a variety of non-canonical functions related to the destruction of various pathogens due to catalytic activity and cofactor effects, the action of antibodies as agonists/antagonists of various receptors, the control of bacterial diversity of the intestine, etc. Canonical and non-canonical functions reflect the extreme human antibody repertoire and the variety of antibody types generated in the organism: antigen-specific, natural, polyreactive, broadly neutralizing, homophilic, bispecific and catalytic. The canonical and non-canonical functions of antibodies greatly enhances the functionality of the human immune system.
  • 937
  • 05 Nov 2020
Topic Review
BET Inhibitors in AIDS Therapy
A critical burden of AIDS therapy is the evasive nature of HIV-1 in face of host immune responses, the so-called “latency.” Recently, a promising approach, the “Shock and Kill” strategy, was proposed to eliminate latently HIV-1-infected cell reservoirs. This therapeutic concept involves two crucial steps: HIV-1 reactivation from its latency stage using a latency-reversing agent (LRA) followed by host immune responses to destroy HIV-1-infected cells in combination with reinforced antiretroviral therapy to kill the progeny virus. Looking at epigenetics of HIV-1 infection, researchers proved that some bromodomains and extra-terminal motif protein inhibitors (BETis) can reactivate HIV-1 from latency. However, to date, only a few BETis have shown HIV-1-reactivating functions, and none of them have yet been approved for clinical trial.  
  • 931
  • 29 Jun 2021
Topic Review
A Novel Innate Immune Regulatory Player: LncRNAs
Long non-coding RNAs (lncRNAs) represent crucial transcriptional and post-transcriptional gene regulators during antimicrobial responses in the host innate immune system. Studies have shown that lncRNAs are expressed in a highly tissue- and cell-specific- manner and are involved in the differentiation and function of innate immune cells, as well as inflammatory and antiviral processes, through versatile molecular mechanisms. These lncRNAs function via the interactions with DNA, RNA, or protein in either cis or trans pattern, relying on their specific sequences or their transcriptions and processing. The dysregulation of lncRNA function is associated with various human non-infectious diseases, such as inflammatory bowel disease, cardiovascular diseases, and diabetes mellitus. Here, we provide an overview of the regulation and mechanisms of lncRNA function in the development and differentiation of innate immune cells, and during the activation or repression of innate immune responses. These elucidations might be beneficial for the development of therapeutic strategies targeting inflammatory and innate immune-mediated diseases.
  • 928
  • 09 Oct 2021
Topic Review
NLRP3 and Preeclampsia
Preeclampsia (PE) is a specific syndrome of human pregnancy, being one of the main causes of maternal death. Persistent inflammation in the endothelium stimulates the secretion of several inflammatory mediators, activating different signaling patterns. One of these mechanisms is related to NLRP3 activation, initiated by high levels of danger signals such as cholesterol, urate, and glucose, producing IL-1, IL-18, and cell death by pyroptosis. Furthermore, reactive oxygen species (ROS), act as an intermediate to activate NLRP3, contributing to subsequent inflammatory cascades and cell damage. Moreover, increased production of ROS may elevate nitric oxide (NO) catabolism and consequently decrease NO bioavailability. NO has many roles in immune responses, including the regulation of signaling cascades. At the site of inflammation, vascular endothelium is crucial in the regulation of systemic inflammation with important implications for homeostasis.
  • 928
  • 19 Nov 2021
Topic Review
Keratin 6, 16 and 17
Located at the skin surface, keratinocytes (KCs) are constantly exposed to external stimuli and are the first responders to invading pathogens and injury. Upon skin injury, activated KCs secrete an array of alarmin molecules, providing a rapid and specific innate immune response against danger signals. However, dysregulation of the innate immune response of KCs may lead to uncontrolled inflammation and psoriasis pathogenesis. Keratins (KRT) are the major structural intermediate filament proteins in KCs and are expressed in a highly specific pattern at different differentiation stages of KCs. While KRT14-KRT5 is restricted to basal proliferative KCs, and KRT10-KRT1 is restricted to suprabasal differentiated KCs in normal skin epidermis, the wound proximal KCs downregulate KRT10-K1 and upregulate KRT16/KRT17-KRT6 upon skin injury. Recent studies have recognized KRT6/16/17 as key early barrier alarmins and upregulation of these keratins alters proliferation, cell adhesion, migration and inflammatory features of KCs, contributing to hyperproliferation and innate immune activation of KCs in response to an epidermal barrier breach, followed by the autoimmune activation of T cells that drives psoriasis. 
  • 928
  • 21 Mar 2022
Topic Review
NLRC4 Inflammasome
The NLR family apoptosis inhibitory proteins (NAIP)-NLR family caspase-associated recruitment domain-containing protein 4 (NLRC4) inflammasome is important for mounting an immune response against Gram-negative bacteria. NLRC4 is activated through NAIPs sensing type 3 secretion system (T3SS) proteins from Gram-negative bacteria, such as Salmonella Typhimurium. Mutations in NAIPs and NLRC4 are linked to autoinflammatory disorders in humans.
  • 925
  • 16 May 2022
Topic Review
EBOV and SARS-CoV-2
Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2 are two highly pathogenic viruses that exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing.
  • 919
  • 07 Feb 2021
Topic Review
Adoptive Immunotherapy beyond CAR T-Cells
The aging of the world population leads to a constant increase of cancer-related morbidity and mortality. Treatment of late-stage tumors has become a significant burden on the healthcare system globally. Adoptive cell immunotherapy is supposed to prolong life with cancer and ideally cure cancer after a single infusion of the cell product. Arguably, the most impressive clinical therapy in this field is based on chimeric antigen receptor (CAR) T-cells capable of curing up to 25–50% of previously incurable patients with B-cell malignancies. Diverse cell therapies are already efficiently used in clinics for cancer treatment (such as tumor infiltrating lymphocytes, transgenic αβ T-cells) and several novel promising cell therapies are in development (such as CAR M-cells, transgenic γδ T-cells, CAR NK-cells). Here, we summarize the recent literature data with the focus on T-cell receptor-based therapies and overview the most advanced systems for manufacturing of clinical grade cell products. 
  • 919
  • 21 Dec 2021
Topic Review
HMGB1
Aneurysmal subarachnoid hemorrhage (aSAH) is a complex and potentially deadly disease. Despite successful obliteration of aneurysm from the circulation, the clinical outcome of aSAH patients is often poor. The reasons for poor outcomes are numerous, including cerebral vasospasm (CVS), post-hemorrhagic hydrocephalus, systemic infections and delayed cerebral ischemia. Although CVS with subsequent cerebral ischemia is one of the main contributors to brain damage after aSAH, little is known about the underlying molecular mechanisms of brain damage. Damaged central nervous system cells release damage-associated molecular pattern molecules (DAMPs) that are important for initiating, driving and sustaining the inflammatory response following an aSAH. The evidence suggested that HMGB1contributes to brain damage during early brain injury and also to the development of CVS during the late phase. Different pharmacological interventions employing natural compounds with HMGB1-antagonizing activity, antibody targeting of HMGB1 or scavenging HMGB1 by soluble receptors for advanced glycation end products (sRAGE), have been shown to dampen the inflammation mediated brain damage and protect against CVS. The experimental data suggest that HMGB1 inhibition is a promising strategy to reduce aSAH-related brain damage and CVS. Clinical studies are needed to validate these findings that may lead to the development of potential treatment options that are much needed in aSAH.
  • 918
  • 28 Oct 2020
Topic Review
Amygdala Neuroinflammation and Psychiatric Disorders
Depression and anxiety disorder are the most common mental diseases affecting hundreds of millions of people worldwide. The comorbidity rate of anxiety disorder and depression is very high, with 74% of depressed patients having anxiety symptoms, while 61% of anxious patients have depression symptoms. Stress exposure is widely accepted as a critical contributing factor to psychological and neuropathological disorders. Especially during the COVID-19 pandemic, the high pressure of increasingly demanding work and life has led to a sharp rise in the incidence of mental diseases. Inflammation induces psychological and neuropathological disorders by influencing neuronal excitability, neurotransmitter release, receptor, and transporter expression through peripheral hormones and autonomic responses. A number of animal and human studies have revealed that the amygdala, ventral hippocampus, and medial prefrontal cortex (mPFC) are extensively involved in the occurrence of anxiety, depression, and related behavioral regulation. Among them, the amygdala, one of the kernel brain regions mediating stress-coping located in the deep temporal lobe, is considered the hub center for processing emotionally salient stimuli and implementing appropriate behavioral responses.
  • 916
  • 23 Feb 2023
Topic Review
Hydroa Vacciniforme, EBV, and Lymphoma
Hydroa vacciniforme (HV) is a rare form of photosensitivity disorder in children or adolescence and is frequently associated with Epstein–Barr virus (EBV) infection, whereas HV-like lymphoproliferative disorders (HVLPD) describe a spectrum of EBV-associated T-cell or natural killer (NK)-cell lymphoproliferations with HV-like cutaneous manifestations, including EBV-positive HV, atypical HV, and HV-like lymphoma. 
  • 915
  • 23 Dec 2020
Topic Review
Nutrients’ Role in Epigenetic Modifications
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by an aberrant immune response and persistent inflammation. Epigenetic changes are dynamic and susceptible to modification in response to environmental stimuli, which provides a feasible intervention to influence epigenetic homeostasis through an “epigenetic diet.” The term epigenetic diet was previously described by Daniel et al., referring to the consumption of certain foods, such as soy, grapes, vegetables, and green tea, which exert mechanisms against aging and cancer. 
  • 912
  • 28 Feb 2023
Topic Review
Extracellular Hsp60, Hsp70 and Hsp90
The role of three members of the Chaperone Systems (CS)—heat shock protein (Hsp)60, Hsp70, and Hsp90—in Immune Systems (IS) modulation and neuroinflammation. These three chaperones occur intra- and extracellularly, with the latter being the most likely involved in neuroinflammation because they can interact with the IS.
  • 910
  • 13 Apr 2021
Topic Review
T Lymphocyte and CAR-T Cell-Derived Extracellular Vesicles
Extracellular vesicles (EV) are a very diverse group of cell-derived vesicles released by almost all kind of living cells. EV are involved in intercellular exchange, both nearby and systemically, since they induce signals and transmit their cargo (proteins, lipids, miRNAs) to other cells, which subsequently trigger a wide variety of biological responses in the target cells. However, cell surface receptor-induced EV release is limited to cells from the immune system, including T lymphocytes. T cell receptor activation of T lymphocytes induces secretion of EV containing T cell receptors for antigen and several bioactive molecules, including proapoptotic proteins. These EV are specific for antigen-bearing cells, which make them ideal candidates for a cell-free, EV-dependent cancer therapy.
  • 905
  • 29 Mar 2022
Topic Review
Dendritic Cell Subsets
Dendritic cells (DCs) constitute a complex network of cell subsets with common functions but also with many divergent aspects. All dendritic cell subsets share the ability to prime T cell response and to undergo a complex trafficking program related to their stage of maturation and function. For these reasons, dendritic cells are implicated in a large variety of both protective and detrimental immune responses, including a crucial role in promoting anti-tumor responses. Although cDC1s are the most potent subset in tumor antigen cross-presentation, they are not sufficient to induce full-strength anti-tumor cytotoxic T cell response and need close interaction and cooperativity with the other dendritic cell subsets, namely cDC2s and pDCs. Here, the functional role of dendritic cell subsets in suppressing tumor growth is discussed. Understanding the specificity of dendritic cell subsets will allow to gain insights on role of these cells in pathological conditions and to design new selective promising therapeutic approaches.
  • 903
  • 05 Nov 2020
Topic Review
CD146 (MCAM)
CD146 is a cell adhesion molecule expressed on all the vascular tree and belongs to the immunoglobulin superfamily. Two isoforms of CD146 exists, a long isoform expressed at the cell junction and a short isoform located at the apical membrane of the cells. CD146 appears to be critical in regulating vascular permeability, cell-cell cohesion, leukocyte transmigration, and angiogenesis. As a consequence, CD146 is involved in the pathogenesis of various diseases including autoimmune diseases and cancers. Also, CD146 exists in a soluble form generated via the action of matrix metalloproteinases and referred to as soluble CD146 (sCD146). The concentration of sCD146 is quantifiable in the sera and cerebrospinal fluid of healthy individuals. Indeed, any variation in its physiological concentration is associated with certain diseases making it an excellent biomarker for diagnostic purposes.  
  • 901
  • 27 Apr 2021
Topic Review
Multispecific Antibodies against Cancer
The principles and current clinical landscape of multispecific antibodies against cancer.
  • 900
  • 07 Jun 2021
Topic Review
Mitogen-Activated Protein Kinases
Influenza A viral (IAV) infections are common, yet persistent as one of the major contributors towards respiratory viral diseases. With the complete eradication of IAVs seemingly impossible, IAV infections are of major public health concern globally as evident by the need for constant surveillance and vaccine renewals. This entry focuses on the innate immune response against influenza infections and in particular, the roles of mitogen-activated protein kinases (MAPKs) in this response. We first detailed the conventional methods of pathogen recognition of influenza viruses by pathogen recognition receptors (PRRs), leading to the activation of pathways involved in the anti-viral response. Predominantly, we have highlighted the roles that MAPKs (ERK, p38 and JNK) play in the activation of Type I Interferons (IFNs) and pro-inflammatory cytokines to resolve IAV infections. Taking a step further, we also looked at how highly pathogenic influenza A viruses (HPIAVs), as well as aberrant and dysfunctional signalling of the MAPK pathways may lead to a hyperactive immune response that is unwarranted, leading to the progression into acute lung injuries and acute respiratory distress syndrome (ARDS) from a simple infection. Taken together, we hope that this entry may shed some light on the important roles that MAPKs play in the innate immune response towards IAV infections, and to provide important considerations when tackling this global challenge.
  • 898
  • 26 Oct 2020
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