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Cellular Immunology

Snigdha Samarpita, Hari Madhuri Doss, Ramamoorthi Ganesan, Mahaboobkhan Rasool
Interleukin 17 (IL-17) and hypoxia have been implicated to play a key role in rheumatoid arthritis (RA). In this study, the combined treatment of IL-17 and cobalt chloride (CoCl2 ), a hypoxia mimetic significantly increased the osteoclast formation and the expression of TRAP and MMP-9 in RAW 264.7 macrophage cells in the presence of RANKL and M-CSF. The unified effect of IL-17 and CoCl2 markedly increased osteoclast mediated bone erosion through the activation of RANKL/NF-κB/NFATc1 signaling pathway. The treatment of IL-17 in combination with CoCl2 further potentiated the protein and mRNA expression of HIF-1α and MMP-9 in rat synovial macrophages...
July 17, 2018: Cellular Immunology
Yasuhiko Kizuka, Sushil Mishra, Yoshiki Yamaguchi, Naoyuki Taniguchi
Glycosylation is profoundly involved in various diseases, and interactions between glycan binding proteins and their sugar ligands are plausible drug targets. Keratan sulfate (KS), a glycosaminoglycan, is downregulated in lungs by cigarette smoking, suggesting that KS is involved in smoking-related diseases, such as chronic obstructive pulmonary disease (COPD). We found that a highly sulfated KS disaccharide, L4, suppresses lung inflammation and is effective against COPD and its exacerbation in mouse models...
July 16, 2018: Cellular Immunology
Isatou Bah, Ajinkya Kumbhare, Lam Nguyen, Charles E McCall, Mohamed El Gazzar
The myeloid-related protein S100A9 reprograms Gr1+ CD11b+ myeloid precursors into myeloid-derived suppressor cells (MDSCs) during murine sepsis. Here, we show that the immunosuppressive cytokine IL-10 supports S100A9 expression and its nuclear localization in MDSCs to function as immune repressors. To support this new concept, we showed that antibody mediated IL-10 blockade in wild-type mice after sepsis induction inhibited MDSC expansion during late sepsis, and that ectopic expression of S100A9 in Gr1+ CD11b+ cells from S100A9 knockout mice switched them into the MDSC phenotype only in the presence of IL-10...
July 11, 2018: Cellular Immunology
Luan Januzi, Jacob W Poirier, Matthew J E Maksoud, Yun-Yan Xiang, Rudolf A W Veldhuizen, Sean E Gill, Sean P Cregan, Haibo Zhang, Gregory A Dekaban, Wei-Yang Lu
In response to micro-environmental cues such as microbial infections or T-helper 1 and 2 (TH 1 and TH 2) cytokines, macrophages (Mϕs) develop into M1- or M2-like phenotypes. Phenotypic polarization/activation of Mϕs are also essentially regulated by autocrine signals. Type-A γ-aminobutyric acid receptor (GABAA R)-mediated autocrine signaling is critical for phenotypic differentiation and transformation of various cell types. The present study explored whether GABAA R signaling regulates lung Mϕ (LMϕ) phenotypic activation under M1/TH 1 and M2/TH 2 environments...
July 7, 2018: Cellular Immunology
Matthias Bock, Christian B Bergmann, Sonja Jung, Miriam Kalbitz, Borna Relja, Stefan Huber-Wagner, Peter Biberthaler, Martijn van Griensven, Marc Hanschen
Platelets modulate the immune system following injury by interacting with CD4+ T regulatory cells (CD4+ Tregs). The underlying mechanisms remain unsolved. We hypothesize paracrine interactions via Tumor necrosis factor-alpha (TNFα)-, Toll like receptor-4 (TLR4)-, and Interleukin-10 (IL-10). In the murine burn injury model, CD4+ Treg activation pathways were selectively addressed using TNFR2-, TLR4- and IL-10-deficient mice. The CD4+ Treg signalling molecule PKC-θ was analyzed using phospho-flow cytometry to detect rapid cell activation...
June 22, 2018: Cellular Immunology
Dmitry D Zhdanov, Yulia A Gladilina, Vadim S Pokrovsky, Dmitry V Grishin, Vladimir A Grachev, Valentina S Orlova, Marina V Pokrovskaya, Svetlana S Alexandrova, Nikolay N Sokolov
Regulatory T cells (Tregs) suppress the activity of effector T, B and NK lymphocytes and sustain immunological tolerance, but the proliferative activity of suppressed cells remains unexplored. In the present study, we report that mouse Tregs can induce replicative senescence and the death of responder mouse CD4+ CD25- T cells, CD8+ T cells, B cells and NK cells in vitro and in vivo. Contact-independent in vitro co-cultivation with Tregs up-regulated endonuclease G (EndoG) expression and its translocation to the nucleus in responder cells...
June 19, 2018: Cellular Immunology
Joanne D Tejero, Nicole C Armand, Caroline M Finn, Kunal Dhume, Tara M Strutt, Karl X Chai, Li-Mei Chen, K Kai McKinstry
Although cigarette smoke is known to alter immune responses, whether and how CD4 T cells are affected is not well-described. We aimed to characterize how exposure to cigarette smoke extract impacts CD4 T cell effector generation in vitro under Th1-polarizing conditions. Our results demonstrate that cigarette smoke directly acts on CD4 T cells to impair effector expansion by decreasing division and increasing apoptosis. Furthermore, cigarette smoke enhances Th1-associated cytokine production and increases expression of the transcription factor T-bet, the master regulator of Th1 differentiation...
June 18, 2018: Cellular Immunology
Subhasis Barik, Mindy Miller, Alexis Cattin-Roy, Tobechukwu Ukah, Habib Zaghouani
IL-13 receptor alpha 1 (IL-13Rα1) associates with IL-4Rα to form a functional IL-4Rα/IL-13Rα1 heteroreceptor (HR) through which both IL-4 and IL-13 signal. Recently, HR expression was associated with the development of M2 type macrophages which function as antigen presenting cells (APCs). Herein, we show that a subset of thymic resident dendritic cells (DCs) expressing high CD11b (CD11bhi ) and intermediate CD11c (CD11cint ) arise in HR-sufficient but not HR-deficient mice. These DCs, which originate from the bone marrow are able to take up Ag from the peritoneum, traffic through the spleen and the lymph nodes and carry it to the thymus...
June 18, 2018: Cellular Immunology
Victoria L Palmer, Alexandra N Worth, Robyn L Scott, Greg A Perry, Mei Yan, Quan-Zhen Li, Patrick C Swanson
IL10 plays a dual role in supporting humoral immunity and inhibiting inflammatory conditions. B cells producing IL10 are thought to play a key regulatory role in maintaining self-tolerance and suppressing excessive inflammation during autoimmune and infectious diseases, primarily by inhibiting associated T cell responses. The extent to which B cells, through the provision of IL10, might function to sustain or inhibit autoantibody production is less clear. We previously described transgenic mice expressing catalytically inactive RAG1 (dnRAG1 mice), which show expansion of an IL10-compentent CD5+ B cell subset that phenotypically resembles B10 B cells, hypogammaglobulinemia, and a restricted B cell receptor repertoire with features indicative of impaired B cell receptor editing...
June 13, 2018: Cellular Immunology
Wenjie Zhang, Ying Ding, Li Sun, Qing Hong, Yumei Sun, Liangliang Han, Mengting Zi, Yuekang Xu
Dendritic cells (DCs) contain heterogeneous populations, with classical DCs developed at steady state and monocyte-derived DCs mobilized under inflammatory conditions, although their total numbers in vivo are scares. To obtain enough quantity for immunological study or clinical application, we have previously established that bone marrow-derived DCs in the presence of Flt-3L (FL-DCs) or GM-CSF (GM-DCs) in vitro are equivalent to the steady state DCs and inflammatory DCs in vivo respectively. What difference, however, exists between these two most commonly used culture systems in DC functions and survival, and how does it correlate to the division of works by their corresponding counterparts in vivo remain ill-defined...
June 7, 2018: Cellular Immunology
Sandhya Bansal, Monal Sharma, Ranjithkumar R, T Mohanakumar
Extracellular vesicles are emerging as potent vehicles of intercellular communication. In this review, we focus on a subclass of extracellular vesicles called exosomes. Previously considered an unimportant catch-all, exosomes have recently been recognized for their role in various diseases and their potential for therapeutic use. We have examined the role of exosomes after human lung transplantation and have delineated the composition of circulating exosomes isolated from lung transplant recipients diagnosed with acute and chronic rejection, primary graft dysfunction, and respiratory viral infection...
June 7, 2018: Cellular Immunology
Elena R Chernykh, Ludmila V Sakhno, Ekaterina Ya Shevela, Marina A Tikhonova, Natalia A Khonina, Alexandr A Ostanin
The engulfment of apoptotic cells by monocytes and unprimed macrophages results in M2 polarization. In the current study, we investigated whether apoptotic cells influence the phenotypic and functional characteristics of GM-CSF-differentiated human macrophages (GM-Mφ). Our results demonstrate that GM-Mφ preincubated with apoptotic neutrophils (GM-MφNeu ) show significantly increased expression of CD206 and FasL and decreased capacity to stimulate allogeneic T-cell proliferation thus adopting M2 features...
June 7, 2018: Cellular Immunology
Tristan de Jesus, Sudhanshu Shukla, Parameswaran Ramakrishnan
O-linked β-N-acetyl glucosamine modification (O-GlcNAcylation) is a dynamic, reversible posttranslational modification of cytoplasmic and nuclear proteins. O-GlcNAcylation depends on nutrient availability and the hexosamine biosynthetic pathway (HBP), which produces the donor substrate UDP-GlcNAc. O-GlcNAcylation is mediated by a single enzyme, O-GlcNAc transferase (OGT), which adds GlcNAc and another enzyme, O-GlcNAcase (OGA), which removes O-GlcNAc from proteins. O-GlcNAcylation controls vital cellular processes including transcription, translation, the cell cycle, metabolism, and cellular stress...
June 2, 2018: Cellular Immunology
Jingyi Jin, Ying Wang, Qianli Ma, Ning Wang, Wenwei Guo, Boquan Jin, Liang Fang, Lihua Chen
Macrophages are key cell types of innate immunity and play a central role in inflammation and host defense. Leukocyte-associated Ig-like receptor-1 (LAIR-1) is highly expressed on macrophages and regulates macrophage functions in several conditions. However, whether LAIR-1 is involved in governing macrophage polarization is still not clear. Here, we investigated the effect of LAIR-1 on macrophage polarization using human macrophage polarization model with THP-1 cells. It was found that LAIR-1 was highly expressed in THP-1 macrophages...
May 31, 2018: Cellular Immunology
Patrícia A F Ribeiro, Daniel S Dias, Daniela P Lage, Lourena E Costa, Vívian T Martins, Grasiele S V Tavares, Débora V C Mendonça, Mariana P Lima, Jamil S Oliveira, Bethina T Steiner, Ricardo A Machado-de-Ávila, Bruno M Roatt, Miguel A Chávez-Fumagalli, Daniel Menezes-Souza, Mariana C Duarte, Antonio L Teixeira, Eduardo A F Coelho
Visceral leishmaniasis (VL) is a fatal disease when acute and untreated. The treatment against this disease is long and presents toxicity and/or high costs. Moreover, parasite resistance has been increasing. Therefore, alternative control measures to avoid the spread of disease should be considered. It is accepted that the development of the T helper (Th)1 immune response, based on the production of pro-inflammatory cytokines, is required for the control of parasites. Although recombinant protein-based vaccines have been tested against VL, they require supplementation with immune adjuvants...
May 29, 2018: Cellular Immunology
Satoshi Nakamizo, Gyohei Egawa, Jasmine Tan Kah Bing, Kenji Kabashima
Various immune cells are present in the skin and modulate the cutaneous immune response. In order to capture such dynamic phenomena, intravital imaging is an important technique and there is a possibility to provide substantial information that is not available using conventional histological analysis. Multiphoton microscope enable direct, three-dimensional, minimally invasive imaging of biological samples with high spatiotemporal resolution, and now become the main method for intravital imaging studies. Here, we will introduce the latest knowledge obtained by intravital imaging of the skin...
May 25, 2018: Cellular Immunology
Xiaotian Xu, Xiaoying Cai, Yingting Zhu, Wen He, Qi Wu, Xiaolei Shi, Yannan Fang, Zhong Pei
Neuroinflammation plays a pivotal role in the incidence and progression of Alzheimer's disease (AD). Cathelicidin-related antimicrobial peptide (CRAMP) is critically involved in the innate neuronal responses of chronic neuroinflammation in AD and thus plays a key role in the disease. Here, we show that Aβ42 induced microglial production of CRAMP, which was effectively inhibited by milk-fat globule-epidermal growth factor 8 (MFG-E8). Production of CRAMP was associated with activation of ERK1/2, p38 and phospho-P65-NF-kB upregulation...
May 24, 2018: Cellular Immunology
Robert J Binder
The intracellular functions of heat shock proteins (HSPs) as chaperones of macromolecules are well known. Current observations point to a role of these chaperones in initiating and modulating immune responses to tumors via receptor(s) on dendritic cells. In this article we provide an insight into, and a basis for, the importance of these HSP-mediated immune responses in rejecting nascent and emerging tumors.
May 16, 2018: Cellular Immunology
Noelia A-Gonzalez, Antonio Castrillo
Macrophage heterogeneity in the spleen has been long documented, with four subsets populating the different splenic compartments. The diverse environments on the splenic compartments determine their varied phenotype and functions. In the white pulp, highly phagocytic macrophages contribute to the generation of the immune response. The marginal zone contains two populations of macrophages, which also contribute to the immune response. Their strategic position in the bloodstream and their unique phenotype confer them a crucial role in the defense against blood borne pathogens, placing them at the crossroad between innate and adaptive immune responses...
May 15, 2018: Cellular Immunology
Jing Wei, Huiyan Sun, Aimei Zhang, Xuejie Wu, Yuxiang Li, Jiawei Liu, Yanting Duan, Fengjun Xiao, Hua Wang, Ming Lv, Lisheng Wang, Chutse Wu
Identifying targets for chimeric antigen receptor-modulated T lymphocyte (CAR-T) therapy against solid tumors is an urgent problem to solve. In this study, we showed for the first time that the receptor tyrosine kinase, AXL, is overexpressed in various tumor cell lines and patient tumor tissues including triple negative breast cancer (TNBC) cell lines and patient samples, making AXL a potent novel target for cancer therapy, specifically for TNBC treatment. We also engineered T cells with a CAR consisting of a novel single-chain variable fragment against AXL and revealed its antigen-specific cytotoxicity and ability to release cytokines in a TNBC cell line and other AXL-positive tumors in vitro...
May 14, 2018: Cellular Immunology
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