Search Results (7)

The most frequent primary cutaneous lymphomas observed in childhood and adolescence are mycosis fungoides (MF) and CD30-positive lymphoproliferative diseases. We report a 22-year-old female who presented with a 6-year history of multiple well-demarcated large roundish-oval scaly and reddish-brownish patches and plaques on the trunk and extremities. Histopathology revealed the focal parakeratosis and prominent epidermotropism of atypical lymphocytes, which were positive for CD8, CD56, and TIA-1 and showed a loss of CD7 and CD5 expression. T-cell receptor (TCR) gene rearrangement analysis (multiplex-PCR, BIOMED-2) of the lesional skin demonstrated the rearrangement of the gamma chain (tube A: 162 nt). Based on clinicopathological findings and a complete work-up, she was diagnosed with juvenile non-poikilodermatous C8+/CD56+ MF in stage IA. Resolution of the skin lesions was achieved by 16-week narrowband UVB phototherapy and clobetasol propionate 0.05% ointment. Juvenile-onset non-poikilodermatous CD8+CD56+ MF represents a very rare MF subtype and is associated with an indolent course. In order to avoid too aggressive diagnostics and treatments, clinicians should be aware of this rare and indolent MF variant in childhood and adolescence. Full article

Numerous nuclear receptors including farnesoid X receptor, liver X receptor, peroxisome proliferator-activated receptors, pregnane X receptor, hepatic nuclear factors have been extensively studied within the context of non-alcoholic fatty liver disease (NAFLD). Following the first description of the Aryl hydrocarbon Receptor (AhR) in the 1970s and decades of research which unveiled its role in toxicity and pathophysiological processes, the functional significance of AhR in NAFLD has not been completely decoded. Recently, multiple research groups have utilized a plethora of in vitro and in vivo models that mimic NAFLD pathology to investigate the functional significance of AhR in fatty liver disease. This review provides a comprehensive account of studies describing both the beneficial and possible detrimental role of AhR in NAFLD. A plausible reconciliation for the paradox indicating AhR as a ‘double-edged sword’ in NAFLD is discussed. Finally, understanding AhR ligands and their signaling in NAFLD will facilitate us to probe AhR as a potential drug target to design innovative therapeutics against NAFLD in the near future. Full article

Contemporary research has found that people with autism spectrum disorder (ASD) exhibit aberrant immunological function, with a shift toward increased cytokine production and unusual cell function. Microglia and astroglia were found to be significantly activated in immuno-cytochemical studies, and cytokine analysis revealed that the macrophage chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and transforming growth factor β-1 (TGFB-1), all generated in the neuroglia, constituted the most predominant cytokines in the brain. Taurine (2-aminoethanesulfonic acid) is a promising therapeutic molecule able to increase the activity of antioxidant enzymes and ATPase, which may be protective against aluminum-induced neurotoxicity. It can also stimulate neurogenesis, synaptogenesis, and reprogramming of proinflammatory M1 macrophage polarization by decreasing mitophagy (mitochondrial autophagy) and raising the expression of the markers of the anti-inflammatory and pro-healing M2 macrophages, such as macrophage mannose receptor (MMR, CD206) and interleukin 10 (IL-10), while lowering the expression of the M1 inflammatory factor genes. Taurine also induces autophagy, which is a mechanism that is impaired in microglia cells and is critically associated with the pathophysiology of ASD. We hypothesize here that taurine could reprogram the metabolism of M1 macrophages that are overstimulated in the nervous system of people suffering from ASD, thereby decreasing the neuroinflammatory process characterized by autophagy impairment (due to excessive microglia activation), neuronal death, and improving cognitive functions. Therefore, we suggest that taurine can serve as an important lead for the development of novel drugs for ASD treatment. Full article

Immune cells are thought to be involved in a destructive cycle of sterile cerebral inflammatory responses in neurodegenerative diseases such as Parkinson’s Disease (PD). Despite their peripheral origin, immune cells may enter the CNS due to impaired blood–brain barrier function and may potentially contribute to neuronal damage. Hence, specific characteristics of peripherally activated immune cells could help in understanding neurodegeneration in PD and could potentially serve as accessible disease markers. To investigate immune cell activation status, the expression of receptors for cell surface molecules CD161, NKG2A, NKG2C and NKG2D as well as chemokine receptors CCR6, CXCR2, CXCR3 and CCR5 associated with neurodegenerative diseases was investigated. The frequencies of peripheral CD8+ T-cells expressing the inhibitory and activating receptors NKG2A and NKG2C, and the activating receptor NKG2D were higher in PD patients than in healthy matched controls. The frequencies of NKG2C+CD8− cells were also higher, whereas the frequencies of CD161+ cells were not significantly different. Of the chemokine receptor-expressing cells, only the proportion of CD4−CD56+CCR5+ T-cells was higher in PD patients than in the controls. These observations support the hypothesis that an imbalance in the activation state of T-cells plays a role in the pathological processes of PD and suggest that peripheral blood immune cell phenotypes could be specific early markers for inflammation in PD. Full article

Multiple myeloma remains an incurable disease despite great advances in its therapeutic landscape. Increasing evidence supports the belief that immune dysfunction plays an important role in the disease pathogenesis, progression, and drug resistance. Recent efforts have focused on harnessing the immune system to exert anti-myeloma effects with encouraging outcomes. First-in-class anti-CD38 monoclonal antibody, daratumumab, now forms part of standard treatment regimens in relapsed and refractory settings and is shifting to front-line treatments. However, a non-negligible number of patients will progress and be triple refractory from the first line of treatment. Antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptors (CAR) are being developed in a heavily pretreated setting with outstanding results. Belantamab mafodotin-blmf has already received approval and other anti-B-cell maturation antigen (BCMA) therapies (CARs and bispecific antibodies are expected to be integrated in therapeutic options against myeloma soon. Nonetheless, immunotherapy faces different challenges in terms of efficacy and safety, and manufacturing and economic drawbacks associated with such a line of therapy pose additional obstacles to broadening its use. In this review, we described the most important clinical data on immunotherapeutic agents, delineated the limitations that lie in immunotherapy, and provided potential insights to overcome such issues. Full article

Natural Killer (NK) cells, an important component of the innate immune system, can mount much more rapid responses upon activation than adaptive antigen specific responses. Among the various functions attributed to NK cells their effect on antibody production merits special attention. The modification of IgG subclasses distribution as well as the amplification of the B cell response can be functionally relevant both for mediation of antibody-dependent cellular cytotoxicity (ADCC) and for control of dysregulated autoantibody production. In this review recent experimental evidence for the mechanistic basis of the effect of NK cells on B cell-responses will be covered. Thus, it will be shown that these effects are mediated not only via activation of cytokine and Toll-like receptors (TLR), but also by direct receptor-ligand interactions. Importantly, the function of these receptor/ligands, CD48 and CD244, do not require recognition of class I-MHC molecules but are more dependent on inflammatory conditions brought about by infection or oncogenesis. Full article

The immune system provides a highly sophisticated surveillance mechanism to detect diverse antigens and protect the host organism from invading pathogens and altered cells (e.g., virus-infected and tumor cells). Adaptive immune responses depend on the recognition of antigen by specific antigen receptors that are expressed on the surface of T and B lymphocytes. Helper T cells provide regulatory functions and direct the adaptive immune system to respond appropriately to a particular antigen (i.e., cytotoxic T cell responses against viral infections and tumor cells, humoral responses against extracellular bacteria and parasitic worms). Helper T cells express CD4 co-receptors, which recognize conserved domains on MHC class II proteins, the same proteins that present antigen to the T cell receptor. Recent progress in T cell biology has identified multiple regulatory functions of the CD4 coreceptor during thymocyte development and antigen stimulation of mature T helper cells. These regulatory functions of CD4 depend on T cell receptor-independent signal transduction. In this review, I discuss the regulation of T cell signaling and emphasize the functional consequences of proper and improper CD4 coreceptor signaling. Full article