scholarly journals RUN and FYVE domain–containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4

2015 ◽  
Vol 210 (7) ◽  
pp. 1133-1152 ◽  
Author(s):  
Seigo Terawaki ◽  
Voahirana Camosseto ◽  
Francesca Prete ◽  
Till Wenger ◽  
Alexia Papadopoulos ◽  
...  
Keyword(s):  
Immune Cells ◽  
Pathogen Detection ◽  
Cell Types ◽  
Interleukin 4 ◽  
Autophagosome Formation ◽  
Autophagy Flux ◽  
Mhc Ii ◽  
Fyve Domain ◽  
Distinct Cell

Autophagy is a key degradative pathway coordinated by external cues, including starvation, oxidative stress, or pathogen detection. Rare are the molecules known to contribute mechanistically to the regulation of autophagy and expressed specifically in particular environmental contexts or in distinct cell types. Here, we unravel the role of RUN and FYVE domain–containing protein 4 (RUFY4) as a positive molecular regulator of macroautophagy in primary dendritic cells (DCs). We show that exposure to interleukin-4 (IL-4) during DC differentiation enhances autophagy flux through mTORC1 regulation and RUFY4 induction, which in turn actively promote LC3 degradation, Syntaxin 17–positive autophagosome formation, and lysosome tethering. Enhanced autophagy boosts endogenous antigen presentation by MHC II and allows host control of Brucella abortus replication in IL-4–treated DCs and in RUFY4-expressing cells. RUFY4 is therefore the first molecule characterized to date that promotes autophagy and influences endosome dynamics in a subset of immune cells.

PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells

Blood ◽  
2000 ◽  
Vol 95 (3) ◽  
pp. 879-885 ◽  
Author(s):  
Anastasia Guerriero ◽  
Peter B. Langmuir ◽  
Lisa M. Spain ◽  
Edward W. Scott
Keyword(s):  
Dendritic Cells ◽  
Interleukin 4 ◽  
Low Density ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Ets Family ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Mixed Lymphocyte Reactions

The ets-family transcription factor PU.1 is required for the proper development of both myeloid and lymphoid progenitors. We used PU.1-deficient animals to examine the role of PU.1 during dendritic cell development. PU.1−/−animals produce lymphoid-derived dendritic cells (DC): low-density class II major histocompatibility complex [MHC-II+] CD11c+ CD8+DEC-205+. But they lack myeloid-derived DC: low-density MHC-II+ CD11c+ CD8−DEC-205−. PU.1−/− embryos also lack progenitors capable of differentiating into myeloid DC in response to granulocyte-macrophage colony-stimulating factor plus interleukin-4. The appearance of lymphoid DC in developing PU.1−/−thymus was initially delayed, but this population recovered to wild type (WT) levels upon organ culture of isolated thymic lobes. PU.1−/−lymphoid DC were functionally equivalent to WT DC for stimulating T-cell proliferation in mixed lymphocyte reactions. These results demonstrate that PU.1 is required for the development of myeloid DC but not lymphoid DC.

Atherosclerosis: cellular mechanisms

2017 ◽  
Author(s):  
Esther Lutgens ◽  
Marie-Luce Bochaton-Piallat ◽  
Christian Weber
Keyword(s):  
Immune Cells ◽  
Adaptive Immune System ◽  
Cell Types ◽  
Chronic Inflammatory Disease ◽  
Branch Points ◽  
Cellular Mechanisms ◽  
Blood Flow Dynamics ◽  
Arterial Intima ◽  
Different Cell Types

Atherosclerosis is a lipid-driven, chronic inflammatory disease of the large and middle-sized arteries that affects every human being and slowly progresses with age. The disease is characterized by the presence of atherosclerotic plaques consisting of lipids, (immune) cells, and debris that form in the arterial intima. Plaques develop at predisposed regions characterized by disturbed blood flow dynamics, such as curvatures and branch points. In the past decades, experimental and patient studies have revealed the role of the different cell-types of the innate and adaptive immune system, and of non-immune cells such as platelets, endothelial, and vascular smooth muscle cells, in its pathogenesis. This chapter highlights the roles of these individual cell types in atherogenesis and explains their modes of communication using chemokines, cytokines, and co-stimulatory molecules.

scholarly journals Intravital 2-photon imaging reveals distinct morphology and infiltrative properties of glioblastoma-associated macrophages

2019 ◽  
Vol 116 (28) ◽  
pp. 14254-14259 ◽  
Author(s):  
Zhihong Chen ◽  
James L. Ross ◽  
Dolores Hambardzumyan
Keyword(s):  
Cell Types ◽  
Lineage Tracing ◽  
Response To Therapy ◽  
Vascular Endothelial ◽  
Distinct Cell ◽  
Attractive Option ◽  
Endothelial Growth Factor ◽  
Distinct Morphology ◽  
Cx3cr1 Expression

Characterized by a dismal survival rate and limited response to therapy, glioblastoma (GBM) remains one of the most aggressive human malignancies. Recent studies of the role of tumor-associated macrophages (TAMs) in the progression of GBMs have demonstrated that TAMs are significant contributors to tumor growth, invasion, and therapeutic resistance. TAMs, which include brain-resident microglia and circulating bone marrow derived-monocytes (BMDMs), are typically grouped together in histopathological and molecular analyses due to the lack of reliable markers of distinction. To develop more effective therapies aimed at specific TAM populations, we must first understand how these cells differ both morphologically and behaviorally. Furthermore, we must develop a deeper understanding of the mechanisms encouraging their infiltration and how these mechanisms can be therapeutically exploited. In this study, we combined immunocompetent lineage tracing mouse models of GBM with high-resolution open-skull 2-photon microscopy to investigate the phenotypical and functional characteristics of TAMs. We demonstrate that TAMs are composed of 2 morphologically distinct cell types that have differential migratory propensities. We show that BMDMs are smaller, minimally branched cells that are highly migratory compared with microglia, which are larger, highly branched stationary cells. In addition, 2 populations of monocytic macrophages were observed that differed in terms of CX3CR1 expression and migratory capacity. Finally, we demonstrate the efficacy of anti-vascular endothelial growth factor A blockade for prohibiting TAM infiltration, especially against BMDMs. Taken together, our data clearly define characteristics of individual TAM populations and suggest that combination therapy with antivascular and antichemotaxis therapy may be an attractive option for treating these tumors.

scholarly journals Role of Immune Cell-Specific Hypermethylation Signatures in Classification and Risk Stratification of Breast Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Yong Chen ◽  
Fada Xia ◽  
Bo Jiang ◽  
Wenlong Wang ◽  
Xinying Li
Keyword(s):  
Breast Cancer ◽  
Risk Stratification ◽  
Immune Cells ◽  
Prediction Accuracy ◽  
Prognostic Value ◽  
Clinical Characteristics ◽  
Immune Cell ◽  
Cell Types ◽  
Clinical Model

Background: Epigenetic regulation, including DNA methylation, plays a major role in shaping the identity and function of immune cells. Innate and adaptive immune cells recruited into tumor tissues contribute to the formation of the tumor immune microenvironment (TIME), which is closely involved in tumor progression in breast cancer (BC). However, the specific methylation signatures of immune cells have not been thoroughly investigated yet. Additionally, it remains unknown whether immune cells-specific methylation signatures can identify subgroups and stratify the prognosis of BC patients.Methods: DNA methylation profiles of six immune cell types from eight datasets downloaded from the Gene Expression Omnibus were collected to identify immune cell-specific hypermethylation signatures (IC-SHMSs). Univariate and multivariate cox regression analyses were performed using BC data obtained from The Cancer Genome Atlas to identify the prognostic value of these IC-SHMSs. An unsupervised clustering analysis of the IC-SHMSs with prognostic value was performed to categorize BC patients into subgroups. Multiple Cox proportional hazard models were constructed to explore the role of IC-SHMSs and their relationship to clinical characteristics in the risk stratification of BC patients. Integrated discrimination improvement (IDI) was performed to determine whether the improvement of IC-SHMSs on clinical characteristics in risk stratification was statistically significant.Results: A total of 655 IC-SHMSs of six immune cell types were identified. Thirty of them had prognostic value, and 10 showed independent prognostic value. Four subgroups of BC patients, which showed significant heterogeneity in terms of survival prognosis and immune landscape, were identified. The model incorporating nine IC-SHMSs showed similar survival prediction accuracy as the clinical model incorporating age and TNM stage [3-year area under the curve (AUC): 0.793 vs. 0.785; 5-year AUC: 0.735 vs. 0.761]. Adding the IC-SHMSs to the clinical model significantly improved its prediction accuracy in risk stratification (3-year AUC: 0.897; 5-year AUC: 0.856). The results of IDI validated the statistical significance of the improvement (p < 0.05).Conclusions: Our study suggests that IC-SHMSs may serve as signatures of classification and risk stratification in BC. Our findings provide new insights into epigenetic signatures, which may help improve subgroup identification, risk stratification, and treatment management.

scholarly journals Role of Immune Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

2020 ◽  
Author(s):  
Sarah Dhaiban ◽  
Mena Al-Ani ◽  
Noha Mousaad Elemam ◽  
Mahmood H Al-Aawad ◽  
Zeinab Al-Rawi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cells ◽  
T Regulatory Cells ◽  
Cell Types ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Chronic Autoimmune Disease ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by varying degrees of demyelination of uncertain etiology, and is associated with specific environmental and genetic factors. Upon recognition of CNS antigens, the immune cells initiate an inflammatory process which leads to destruction and deterioration of the neurons. Innate immune cells such as macrophages, dendritic cells and natural killer cells are known to play critical roles in the pathogenesis of MS. Also, the activation of peripheral CD4+ T cells by CNS antigens leads to their extravasation into the CNS causing damages that exacerbates the disease. This could be accompanied by dysregulation of T regulatory cells and other cell types functions. Experimental autoimmune encephalomyelitis (EAE) is a mouse model used to study the pathophysiology of MS disease. In this review, we highlight the roles of innate and adaptive immune players in the pathogenesis of MS and EAE.

scholarly journals An Opaque Cell-Specific Expression Program of Secreted Proteases and Transporters Allows Cell-Type Cooperation in Candida albicans

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 409-429
Author(s):  
Matthew B. Lohse ◽  
Lucas R. Brenes ◽  
Naomi Ziv ◽  
Michael B. Winter ◽  
Charles S. Craik ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Opportunistic Pathogen ◽  
Cell Types ◽  
Specific Expression ◽  
Environmental Signals ◽  
Single Genome ◽  
Distinct Cell ◽  
Secreted Proteases ◽  
Expression Program

An unusual feature of the opportunistic pathogen Candida albicans is its ability to switch stochastically between two distinct, heritable cell types called white and opaque. Here, we show that only opaque cells, in response to environmental signals, massively upregulate a specific group of secreted proteases and peptide transporters, allowing exceptionally efficient use of proteins as sources of nitrogen. We identify the specific proteases [members of the secreted aspartyl protease (SAP) family] needed for opaque cells to proliferate under these conditions, and we identify four transcriptional regulators of this specialized proteolysis and uptake program. We also show that, in mixed cultures, opaque cells enable white cells to also proliferate efficiently when proteins are the sole nitrogen source. Based on these observations, we suggest that one role of white-opaque switching is to create mixed populations where the different phenotypes derived from a single genome are shared between two distinct cell types.

The role of SLAM family receptors in immune cell signalingThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Membrane Proteins in Health and Disease.

2006 ◽  
Vol 84 (6) ◽  
pp. 832-843 ◽  
Author(s):  
Elena A. Ostrakhovitch ◽  
Shawn S.-C. Li
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Critical Role ◽  
Cell Types ◽  
Health And Disease ◽  
Slam Family ◽  
Different Cell Types ◽  
Selection Of

The signaling lymphocyte-activating molecule (SLAM) family immunoreceptors are expressed in a wide array of immune cells, including both T and B lymphocytes. By virtue of their ability to transduce tyrosine phosphorylation signals through the so-called ITSM (immunoreceptor tyrosine-based switch motif) sequences, they play an important part in regulating both innate and adaptive immune responses. The critical role of the SLAM immunoreceptors in mediating normal immune reactions was highlighted in recent findings that SAP, a SLAM-associated protein, modulates the activities of various immune cells through interactions with different members of the SLAM family expressed in these cells. Importantly, mutations or deletions of the sap gene in humans result in the X-linked lymphoproliferative syndrome. In this review, we summarize current knowledge and survey the latest developments in signal transduction events triggered by the activation of SLAM family receptors in different cell types.

scholarly journals The Role of Dendritic Cells during Physiological and Pathological Dentinogenesis

2021 ◽  
Vol 10 (15) ◽  
pp. 3348
Author(s):  
Angela Quispe-Salcedo ◽  
Hayato Ohshima
Keyword(s):  
Dendritic Cells ◽  
Cell Types ◽  
Tooth Injuries ◽  
Tertiary Dentin ◽  
Distinct Cell ◽  
Reparative Dentin ◽  
Pulp Cells ◽  
Antigen Presenting

The dental pulp is a soft connective tissue of ectomesenchymal origin that harbors distinct cell populations, capable of interacting with each other to maintain the vitality of the tooth. After tooth injuries, a sequence of complex biological events takes place in the pulpal tissue to restore its homeostasis. The pulpal response begins with establishing an inflammatory reaction that leads to the formation of a matrix of reactionary or reparative dentin, according to the nature of the exogenous stimuli. Using several in vivo designs, antigen-presenting cells, including macrophages and dendritic cells (DCs), are identified in the pulpal tissue before tertiary dentin deposition under the afflicted area. However, the precise nature of this phenomenon and its relationship to inherent pulp cells are not yet clarified. This literature review aims to discuss the role of pulpal DCs and their relationship to progenitor/stem cells, odontoblasts or odontoblast-like cells, and other immunocompetent cells during physiological and pathological dentinogenesis. The concept of “dentin-pulp immunology” is proposed for understanding the crosstalk among these cell types after tooth injuries, and the possibility of immune-based therapies is introduced to accelerate pulpal healing after exogenous stimuli.

scholarly journals A Novel Inflammatory Dendritic Cell That Is Abundant and Contiguous to T Cells in the Kidneys of Patients With Lupus Nephritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Samir V. Parikh ◽  
Ana Malvar ◽  
John Shapiro ◽  
James M. Turman ◽  
Huijuan Song ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cell ◽  
Lupus Nephritis ◽  
Immune Cells ◽  
Kidney Injury ◽  
Cell Types ◽  
Gamma Chain ◽  
Healthy Human ◽  
Mhc Ii ◽  
Confocal Immunofluorescence

The mechanisms that promote local inflammatory injury during lupus nephritis (LN) flare are largely unknown. Understanding the key immune cells that drive intrarenal inflammation will advance our knowledge of disease pathogenesis and inform the development of new therapeutics for LN management. In this study, we analyzed kidney biopsies from patients with proliferative LN and identified a novel inflammatory dendritic cell (infDC) population that is highly expressed in the LN kidney, but minimally present in healthy human kidneys. During an agnostic evaluation of immune transcript expression in the kidneys of patients with proliferative LN, the most abundantly overexpressed transcript from isolated glomeruli was FCER1G, which encodes the Fc receptor gamma chain (FcRγ). To identify the cell types expressing FcRγ that infiltrate the kidney in LN, studies were done on kidney biopsies from patients with active LN using confocal immunofluorescence (IF) microscopy. This showed that FcRγ is abundantly present in the periglomerular (PG) region of the kidney and to a lesser extent in the tubulointerstitium (TI). Further investigation of the surface markers of these cells showed that they were FcRγ+, MHC II+, CD11c+, CD163+, CD5−, DC-SIGN+, CD64+, CD14+, CD16+, SIRPα+, CD206−, CD68−, CD123−, CD3−, and CD11b−, suggesting the cells were infDCs. Quantification of the infDCs showed an average 10-fold higher level of infDCs in the LN kidney compared to the healthy kidneys. Importantly, IF identified CD3+ T cells to be adjacent to these infDCs in the PG space of the LN kidney, whereas both cell types are minimally present in the healthy kidney. Thus, we have identified a previously undescribed DC in lupus kidneys that may interact with intrarenal T cells and play a role in the pathogenesis of kidney injury during LN flare.

scholarly journals Integrins alpha v beta 3 and alpha v beta 5 contribute to cell attachment to vitronectin but differentially distribute on the cell surface.

1991 ◽  
Vol 113 (4) ◽  
pp. 919-929 ◽  
Author(s):  
E A Wayner ◽  
R A Orlando ◽  
D A Cheresh
Keyword(s):  
Cell Surface ◽  
Lung Carcinoma ◽  
Cell Attachment ◽  
Cell Types ◽  
Carcinoma Cells ◽  
Lung Carcinoma Cells ◽  
Distinct Cell ◽  
Contact Distribution ◽  
Alpha V Beta 3

We investigated the role of the integrins alpha v beta 3 and alpha v beta 5 in mediating vitronectin adhesion of three phenotypically distinct cell types. M21 human melanoma cells and H2981 lung carcinoma cells use both alpha v-containing integrins in adhering to vitronectin while UCLA-P3 lung carcinoma cells adhere exclusively with alpha v beta 5. Specifically, monoclonal antibodies directed to functional epitopes on both receptors were required to block adhesion of M21 or H2981 cells while adhesion of UCLA-P3 cells to vitronectin could be blocked with a monoclonal antibody to alpha v beta 5. Although both receptors are involved in M21 and H2981 cell adhesion to vitronectin, only alpha v beta 3 can be detected in focal contacts, colocalizing with vinculin, talin, and the ends of actin filaments, while alpha v beta 5 shows a distinct, nonfocal contact, distribution on the cell surface. These results provide the first evidence that two homologous integrins that recognize the same ligand distribute differentially on the cell surface.

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