scholarly journals Involvement of the CD95 (APO-1/Fas) receptor/ligand system in multiple sclerosis brain.

1996 ◽  
Vol 184 (4) ◽  
pp. 1513-1518 ◽  
Author(s):  
P Dowling ◽  
G Shang ◽  
S Raval ◽  
J Menonna ◽  
S Cook ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Fas Ligand ◽  
Cell Types ◽  
Receptor Expression ◽  
Fas Receptor ◽  
Ligand System ◽  
Fas L ◽  
Dying Cells ◽  
Different Cell Types

Immunohistochemical methods were used to search for Fas receptor/Fas ligand system involvement in multiple sclerosis (MS) white matter brain lesions. We found large numbers of Fas ligand (Fas-L)-bearing cells present in two acute lesions and 12 of 16 chronic MS lesions, and very few positive cells in non-inflammatory controls. Four of six brains from non-MS neuropathologic conditions associated with inflammation and white matter disease were, however, also positive for Fas-L. Double staining with cell-specific markers revealed that the pattern of ligand-positive cells in chronic MS lesions was complex and composed of several different cell types which were primarily resident glial cells with a small overlay of macrophages. Fas/APO 1 (CD95) receptor expression in MS tissue was also evaluated and marked upregulation of the receptor was found. In addition, Fas receptor was induced, but to a lesser extent, in numerous control brains. The observations that TUNEL-positive dying cells were present in MS lesions and showed excellent co-localization with Fas-L, indicate that the Fas death system may contribute to plaque pathogenesis and could lead to the development of a new category of therapeutic agents for MS.

Differential Sensitivity of CD4+ and CD8+T Lymphocytes to the Killing Efficacy of Fas (Apo-1/CD95) Ligand+ Tumor Cells in B Chronic Lymphocytic Leukemia

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4273-4281 ◽  
Author(s):  
Inge Tinhofer ◽  
Ingrid Marschitz ◽  
Marion Kos ◽  
Traudl Henn ◽  
Alexander Egle ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Line ◽  
Tumor Cells ◽  
Fas Ligand ◽  
Lymphocytic Leukemia ◽  
Receptor Expression ◽  
Differential Sensitivity ◽  
Relative Reduction ◽  
Cd4 Cells ◽  
Fas Receptor

Abstract B-chronic lymphocytic leukemia (B-CLL) is characterized by cellular and humoral immune defects resulting in increased rates of infection and disturbed immune surveillance against cancer cells as well as by the expansion of slowly proliferating tumor cells. We found increased Fas receptor (FasR) expression in peripheral blood CD4+and CD8+ cells of B-CLL patients compared with the equivalent cells of healthy donors. Although increased Fas receptor expression was significant in both T-lymphocytic subsets, only CD4+ cells from B-CLL patients underwent apoptosis after treatment with the agonistic Fas antibody CH11. In CD4+cells of B-CLL patients, the Fas-sensitivity also correlated with a CD4+/CD8+ ratio below the lower threshold of healthy individuals (<1.0). By contrast, FasR expression in the CD19+ fraction of B-CLL patients was downregulated compared with normal controls, and this was associated with an insensitivity to CH11-induced apoptosis. The B-CLL cell line EHEB as well as CD19+ cells from B-CLL patients constitutively expressed Fas ligand (FasL). The FasL was functionally active, as the B-CLL cell line as well as T-cell–depleted CD19+ B-CLL fractions were able to kill target T-acute lymphatic leukemia (T-ALL) cells in vitro. This effect was inhibited by the antagonistic FasR-antibody ZB4, the neutralizing anti-FasL monoclonal antibody (MoAb) NOK-2 or by transfection of the caspase inhibitor crmA. These data point to the fact that expression of FasL on CD19+B-CLL cells, together with enhanced susceptibility of CD4+ T cells toward FasL-bearing effector cells, are causally linked to the relative reduction of CD4+ cells occurring during B-CLL progression. These findings could explain the inversion of the ratio of CD4+/CD8+ cell numbers, which may be causally linked to the immune deficiency observed in these patients and to the expansion of the neoplastic clone in B-CLL.

scholarly journals The Role of MicroRNAs in Repair Processes in Multiple Sclerosis

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1711 ◽  
Author(s):  
Conor P. Duffy ◽  
Claire E. McCoy
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Disorder ◽  
Cell Types ◽  
Repair Process ◽  
Rna Molecules ◽  
Current State ◽  
Non Coding Rna ◽  
Repair Mechanisms ◽  
Different Cell Types

Multiple sclerosis (MS) is an autoimmune disorder characterised by demyelination of central nervous system neurons with subsequent damage, cell death and disability. While mechanisms exist in the CNS to repair this damage, they are disrupted in MS and currently there are no treatments to address this deficit. In recent years, increasing attention has been paid to the influence of the small, non-coding RNA molecules, microRNAs (miRNAs), in autoimmune disorders, including MS. In this review, we examine the role of miRNAs in remyelination in the different cell types that contribute to MS. We focus on key miRNAs that have a central role in mediating the repair process, along with several more that play either secondary or inhibitory roles in one or more aspects. Finally, we consider the current state of miRNAs as therapeutic targets in MS, acknowledging current challenges and potential strategies to overcome them in developing effective novel therapeutics to enhance repair mechanisms in MS.

Prognostic significance of the Fas-receptor/Fas-ligand system in cervical squamous cell carcinoma

2007 ◽  
Vol 452 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Enrique Lerma ◽  
Marisa Romero ◽  
Alberto Gallardo ◽  
Cristina Pons ◽  
Josefina Muñoz ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Fas Ligand ◽  
Prognostic Significance ◽  
Cervical Squamous Cell Carcinoma ◽  
Fas Receptor ◽  
Ligand System

scholarly journals Tumor Rejection by Disturbing Tumor Stroma Cell Interactions

2001 ◽  
Vol 194 (11) ◽  
pp. 1549-1560 ◽  
Author(s):  
Sabrina Ibe ◽  
Zhihai Qin ◽  
Thomas Schüler ◽  
Susanne Preiss ◽  
Thomas Blankenstein
Keyword(s):  
T Cells ◽  
Tumor Stroma ◽  
Residual Tumor ◽  
Cell Types ◽  
Cell Interactions ◽  
Tumor Rejection ◽  
Receptor Expression ◽  
Stroma Cell ◽  
Ifn Γ ◽  
Different Cell Types

The stroma of solid tumors is a complex network of different cell types. We analyzed stroma cell interactions in two tumor models during cyclophosphamide (Cy)-induced tumor rejection. In growing tumors, tumor infiltrating macrophages (TIMs) produced interleukin (IL)-10. Beginning 6 h after Cy-treatment T cells in the tumor were inactivated and TIMs switched to interferon (IFN)-γ production. Both, IL-10 production before and IFN-γ production after Cy-treatment by TIMs required T cells. With the same kinetics as TIMs started to produce IFN-γ the tumor vasculature was destroyed which required IFN-γ receptor expression on host but not tumor cells. These events preceded hemorrhagic necrosis and residual tumor cell elimination by T cells. Together, T cells regulate the function of TIMs and tumor rejection can be induced by disturbing the stroma network.

scholarly journals A genetic, genomic, and computational resource for exploring neural circuit function

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Fred P Davis ◽  
Aljoscha Nern ◽  
Serge Picard ◽  
Michael B Reiser ◽  
Gerald M Rubin ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Neural Circuit ◽  
Individual Cell ◽  
Probabilistic Method ◽  
Expression Patterns ◽  
Cell Types ◽  
Receptor Expression ◽  
Generating Functional ◽  
Circuit Function ◽  
Different Cell Types

The anatomy of many neural circuits is being characterized with increasing resolution, but their molecular properties remain mostly unknown. Here, we characterize gene expression patterns in distinct neural cell types of the Drosophila visual system using genetic lines to access individual cell types, the TAPIN-seq method to measure their transcriptomes, and a probabilistic method to interpret these measurements. We used these tools to build a resource of high-resolution transcriptomes for 100 driver lines covering 67 cell types, available at http://www.opticlobe.com. Combining these transcriptomes with recently reported connectomes helps characterize how information is transmitted and processed across a range of scales, from individual synapses to circuit pathways. We describe examples that include identifying neurotransmitters, including cases of apparent co-release, generating functional hypotheses based on receptor expression, as well as identifying strong commonalities between different cell types.

scholarly journals A genetic, genomic, and computational resource for exploring neural circuit function

2018 ◽  
Author(s):  
Fred P. Davis ◽  
Aljoscha Nern ◽  
Serge Picard ◽  
Michael B. Reiser ◽  
Gerald M. Rubin ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Affinity Purification ◽  
Probabilistic Method ◽  
Expression Patterns ◽  
Cell Types ◽  
Receptor Expression ◽  
List Type ◽  
Visual Neurons ◽  
Circuit Function ◽  
Different Cell Types

AbstractThe anatomy of many neural circuits is being characterized with increasing resolution, but their molecular properties remain mostly unknown. Here, we characterize gene expression patterns in distinct neural cell types of the Drosophila visual system using genetic lines to access individual cell types, the TAPIN-seq method to measure their transcriptomes, and a probabilistic method to interpret these measurements. We used these tools to build a resource of high-resolution transcriptomes for 100 driver lines covering 67 cell types, available at http://www.opticlobe.com. Combining these transcriptomes with recently reported connectomes helps characterize how information is transmitted and processed across a range of scales, from individual synapses to circuit pathways. We describe examples that include identifying neurotransmitters, including cases of co-release, generating functional hypotheses based on receptor expression, as well as identifying strong commonalities between different cell types.HighlightsTranscriptomes reveal transmitters and receptors expressed in Drosophila visual neuronsTandem affinity purification of intact nuclei (TAPIN) enables neuronal genomicsTAPIN-seq and genetic drivers establish transcriptomes of 67 Drosophila cell typesProbabilistic modeling simplifies interpretation of large transcriptome catalogs

Localization of Angiotensin II Type 1 receptor gene expression in rodent and human kidneys

2021 ◽  
Author(s):  
Julia Schrankl ◽  
Michaela Fuchs ◽  
Katharina Broeker ◽  
Christoph Daniel ◽  
Armin Kurtz ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Mesangial Cells ◽  
Vascular System ◽  
Receptor Gene ◽  
Cell Types ◽  
Receptor Expression ◽  
Ang Ii ◽  
Comprehensive Overview ◽  
Different Cell Types

The kidneys are an important target for angiotensin II (ANG II). In the adult kidneys the effects of ANG II are mediated mainly by ANG II type 1 (AT1) receptors. AT1 receptor expression has been reported for a variety of different cell types within the kidneys, suggesting a broad spectrum of actions for ANG II. Since there have been heterogeneous results in the literature regarding the intrarenal distribution of AT1 receptors, this study aimed to obtain a comprehensive overview about the localization of AT1 receptor expression in mouse, rat and human kidneys. Using the cell specific and high-resolution RNAscope technique, we performed colocalization studies with various cell markers to specifically discriminate between different segments of the tubular and vascular system. Overall we found a similar pattern of AT1 mRNA expression in mouse, rat and human kidneys. AT1 receptors were detected in mesangial cells and renin-producing cells. In addition, AT1 mRNA was found in interstitial cells of the cortex and outer medulla. In rodents, late afferent and early efferent arterioles expressed AT1 receptor mRNA, but larger vessels of the investigated species showed no AT1 expression. Tubular expression of AT1 mRNA was species-dependent with a strong expression in proximal tubules of mice while expression was undetectable in human tubular cells. These findings suggest that the (juxta)glomerular area and the tubulointerstitium are conserved expression sites for AT1 receptors across species and might present the main target sites for ANG II in adult human and rodent kidneys.

scholarly journals Role of Fas Ligand and Receptor in the Mechanism of T-Cell Depletion in Acquired Immunodeficiency Syndrome: Effect on CD4+ Lymphocyte Depletion and Human Immunodeficiency Virus Replication

Blood ◽  
1997 ◽  
Vol 89 (4) ◽  
pp. 1357-1363 ◽  
Author(s):  
E.M. Sloand ◽  
N.S. Young ◽  
P. Kumar ◽  
F.F. Weichold ◽  
T. Sato ◽  
...  
Keyword(s):  
Fas Ligand ◽  
Cd4 Cells ◽  
Fas Receptor ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Fas L ◽  
Immunodeficiency Syndrome ◽  
Hiv 1 ◽  
Normal Controls

Abstract Direct killing of CD4+ lymphocytes by human immunodeficiency virus-1 (HIV-1) probably cannot account for the magnitude of the loss of these cells during the course of HIV-1 infection. Experimental evidence supports a pathophysiologic role of the apoptotic process in depletion of CD4 cells in acquired immunodeficiency syndrome (AIDS). The Fas-receptor/Fas-ligand (Fas-R/Fas-L) system mediates signals for apoptosis of susceptible lymphocytes and lympoblastoid cell lines. A number of investigators have recently reported increased expression of the Fas receptor in individuals with HIV infection, along with increased sensitivity of their lymphocytes to anti-Fas antibody mimicking Fas ligand. We attempted to determine the role of Fas-mediated apoptosis in disease progression and viral replication. Increased Fas-receptor (CD95) expression on CD4+ and CD8+ lymphocytes was found in a large group of HIV-1–infected patients compared with normal controls; individuals with a diagnosis of AIDS and a history of opportunistic infection had significantly more Fas receptor expression than did asymptomatic HIV-infected persons and normal blood donor controls (P < .01). Triggering of the Fas-R by agonistic anti-Fas monoclonal antibody, CH11, was preferentially associated with apoptosis in the CD4+ cells; this effect was more pronounced in lymphocytes derived from HIV+ individuals. Soluble and membrane-bound forms of Fas-L were produced in greater amounts in peripheral blood mononuclear cells (PBMC) cultures and in plasma obtained from HIV-1–infected persons than from normal controls. Furthermore, triggering of lymphocytes from HIV-infected persons by CH11 increased levels of interleukin-1β converting enzyme (ICE), a protein associated with apoptosis. When PBMC were cultured in the presence of CH11, p24 production per number of viable cells was decreased as compared with the same PBMC without CH11 (P < .01). These findings suggest that multiple mechanisms, including increased production of Fas-L by infected PBMC, increased Fas-R expression, and induction of a protease of ICE family, may play roles in the apoptotic depletion of CD4+ cells in HIV infection.

scholarly journals Cytokines and Fas regulate apoptosis in murine renal interstitial fibroblasts.

1997 ◽  
Vol 8 (12) ◽  
pp. 1845-1854
Author(s):  
A Ortiz ◽  
C Lorz ◽  
S González-Cuadrado ◽  
R Garcia del Moral ◽  
F O'Valle ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Fas Ligand ◽  
Apoptotic Cell ◽  
Physiological Mechanism ◽  
Serum Deprivation ◽  
Receptor Expression ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Fas Receptor ◽  
Fas Mrna

Renal fibrosis is characterized by an increased number of fibroblasts and excessive deposition of extracellular matrix. Apoptotic cell death is a physiological mechanism to limit cell numbers, and an insufficient rate of death may contribute to fibroblast accumulation. However, little is known about the regulation of renal fibroblast survival. The authors have studied the interaction of cytokines and the Fas receptor in the regulation of apoptosis of renal fibroblasts and have observed that murine renal fibroblasts express Fas and the Fas ligand. Tumor necrosis factor alpha (TNFalpha) and agonistic anti-Fas antibodies induce apoptosis of renal fibroblasts in a time- and dose-dependent manner. Serum contains survival factors for renal fibroblasts. Both serum deprivation and TNFalpha increase the sensitivity to Fas-induced death and the expression of fas mRNA and Fas receptor. By contrast, insulin-like growth factor-1 decreases apoptosis induced by both serum deprivation and Fas activation and partially prevents the increase in Fas receptor expression induced by serum deprivation. Murine renal fibroblasts express constitutively both fas ligand mRNA and cell-surface Fas ligand, but the authors could not demonstrate a role for Fas ligand in the autocrine regulation of fibroblast survival. These data suggest that Fas and other cytokines cooperate to regulate renal fibroblast apoptosis. Modulation of the Fas death-signaling pathway in renal fibroblasts could represent a new therapeutic target for renal fibrosis.

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