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https://www.readbyqxmd.com/read/28940186/an-r848-adjuvanted-influenza-vaccine-promotes-early-activation-of-b-cells-in-the-draining-lymph-node-of-nonhuman-primate-neonates
#1
Beth C Holbrook, S Tyler Aycock, Emily Machiele, Elene Clemens, Danielle Gries, Matthew J Jorgensen, Mallinath B Hadimani, S Bruce King, Martha A Alexander-Miller
Impaired immune responsiveness is a significant barrier to vaccination of neonates. By way of example, the low seroconversion observed following influenza vaccination has led to restriction of its use to infants over 6 months of age, leaving younger infants vulnerable to infection. Our previous studies using a nonhuman primate neonate model demonstrated that the immune response elicited following vaccination with inactivated influenza virus could be robustly increased by inclusion of the TLR agonist flagellin or R848, either delivered individually or in combination...
September 22, 2017: Immunology
https://www.readbyqxmd.com/read/28938397/regulation-of-orbital-fibrosis-and-adipogenesis-by-pathogenic-th17-cells-in-graves-orbitopathy
#2
Sijie Fang, Yazhuo Huang, Sisi Zhong, Yangyang Li, Yidan Zhang, Yinwei Li, Jing Sun, Xingtong Liu, Yang Wang, Shuo Zhang, Tianle Xu, Xiaodong Sun, Ping Gu, Dan Li, Huifang Zhou, Bin Li, Xianqun Fan
Context: Th17 cells are correlated with many human autoimmune disorders including Graves' disease, and may play key roles in the pathogenesis of Graves' orbitopathy (GO). Objective: To study the phenotype of Th17 cells in patients with GO and healthy subjects, investigate the fibrosis and adipogenesis in orbital fibroblasts (OFs) modulated by IL-17A, and determine the interaction between Th17 cells and OFs. Design/Setting/Participants: Blood samples and orbital tissues from GO patients and healthy controls were collected...
August 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28936211/regulation-of-human-macrophage-m1-m2-polarization-balance-by-hypoxia-and-the-triggering-receptor-expressed-on-myeloid-cells-1
#3
Federica Raggi, Simone Pelassa, Daniele Pierobon, Federica Penco, Marco Gattorno, Francesco Novelli, Alessandra Eva, Luigi Varesio, Mirella Giovarelli, Maria Carla Bosco
Macrophages (Mf) are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1) and alternatively activated (anti-inflammatory M2) subsets...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28935250/engineered-cells-for-costimulatory-enhancement-combined-with-il-21-enhance-the-generation-of-pd-1-disrupted-ctls-for-adoptive-immunotherapy
#4
Jie Shao, Qiuping Xu, Shu Su, Fanyan Meng, Zhengyun Zou, Fangjun Chen, Juan Du, Xiaoping Qian, Baorui Liu
Blockade of the immune cell checkpoint inhibitors programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) has become a powerful tool in cancer treatment, which is effective across various solid cancer types and hematologic malignancies. Our previous studies showed that by reducing immune tolerance, clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) modified cytotoxic T lymphocytes (CTLs) rank highly in terms of immune responses and cytotoxicity. In this study, a genetically modified K562 cell line with surface expression of 4-1BBL was developed to expand PD-1-disrupted CTLs in vitro for further adoptive immunotherapy against cancer...
September 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28932638/the-anti-slamf7-antibody-elotuzumab-mediates-nk-cell-activation-through-both-cd16-dependent-and-independent-mechanisms
#5
Tatiana Pazina, Ashley M James, Alexander W MacFarlane, Natalie A Bezman, Karla A Henning, Christine Bee, Robert F Graziano, Michael D Robbins, Adam D Cohen, Kerry S Campbell
Elotuzumab is a humanized therapeutic monoclonal antibody directed to the surface glycoprotein SLAMF7 (CS1, CRACC, CD319), which is highly expressed on multiple myeloma (MM) tumor cells. Improved clinical outcomes have been observed following treatment of MM patients with elotuzumab in combination with lenalidomide or bortezomib. Previous work showed that elotuzumab stimulates NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), via Fc-domain engagement with FcγRIIIa (CD16). SLAMF7 is also expressed on NK cells, where it can transmit stimulatory signals...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931462/paradoxical-development-of-polymyositis-like-autoimmunity-through-augmented-expression-of-autoimmune-regulator-aire
#6
Hitoshi Nishijima, Tatsuya Kajimoto, Yoshiki Matsuoka, Yasuhiro Mouri, Junko Morimoto, Minoru Matsumoto, Hiroshi Kawano, Yasuhiko Nishioka, Hisanori Uehara, Keisuke Izumi, Koichi Tsuneyama, Il-Mi Okazaki, Taku Okazaki, Kazuyoshi Hosomichi, Ayako Shiraki, Makoto Shibutani, Kunitoshi Mitsumori, Mitsuru Matsumoto
Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs...
September 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28929455/role-of-mast-cells-in-regulation-of-t-cell-responses-in-experimental-and-clinical-settings
#7
REVIEW
Daniel Elieh Ali Komi, Korneel Grauwet
Mast cells secrete a wide spectrum of stored or newly synthesized pro-inflammatory, anti-inflammatory, and/or immunosuppressive mediators and express several costimulatory and inhibitory surface molecules. Mast cells finely tune activities of T cells, B cells, and regulatory cells and effectively contribute to the development of different T cell-associated responses by influencing their recruitment, activation, proliferation, and differentiation. The interaction between mast cells and T cells, with regard to cellular functionality and immune responses, can be assessed in both activating and inhibitory regulations...
September 19, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28928741/cxcl12-mediates-aberrant-costimulation-of-b-lymphocytes-in-warts-hypogammaglobulinemia-infections-myelokathexis-immunodeficiency
#8
Giuliana Roselli, Elisa Martini, Vassilios Lougaris, Raffaele Badolato, Antonella Viola, Marinos Kallikourdis
The Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) syndrome is an immunodeficiency caused by mutations in chemokine receptor CXCR4. WHIM patient adaptive immunity defects remain largely unexplained. We have previously shown that WHIM-mutant T cells form unstable immunological synapses, affecting T cell activation. Here, we show that, in WHIM patients and WHIM CXCR4 knock-in mice, B cells are more apoptosis prone. Intriguingly, WHIM-mutant B cells were also characterized by spontaneous activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#9
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28913366/the-differential-contribution-of-the-innate-immune-system-to-a-good-pathological-response-in-the-breast-and-axillary-lymph-nodes-induced-by-neoadjuvant-chemotherapy-in-women-with-large-and-locally-advanced-breast-cancers
#10
Viriya Kaewkangsadan, Chandan Verma, Jennifer M Eremin, Gerard Cowley, Mohammad Ilyas, Sukchai Satthaporn, Oleg Eremin
The tumour microenvironment consists of malignant cells, stroma, and immune cells. The role of adaptive immunity in inducing a pathological complete response (pCR) in breast cancer with neoadjuvant chemotherapy (NAC) is well studied. The contribution of innate immunity, however, is poorly documented. Breast tumours and axillary lymph nodes (ALNs) from 33 women with large and locally advanced breast cancers (LLABCs) undergoing NAC were immunohistochemically assessed for tumour-infiltrating macrophages (TIMs: M1 and M2), neutrophils (TINs), and dendritic cells (TIDCs) using labelled antibodies and semiquantitative methods...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28904313/immune-receptors-cd40-and-cd86-in-oral-keratinocytes-and-implications-for-oral-lichen-planus
#11
Alison Marshall, Antonio Celentano, Nicola Cirillo, Michiko Mirams, Michael McCullough, Stephen Porter
Lichen planus (LP) is a chronic T-cell-mediated mucocutaneous inflammatory disease that targets stratified epithelia, including those lining the oral cavity. The intraoral variant of LP (OLP) is associated with interferon (IFN)-γ production by infiltrating T lymphocytes; however, the role of epithelial cells in the etiopathogenesis OLP is not completely understood. There is however a growing body of evidence regarding the involvement of epithelial-derived cytokines, immune receptors, and costimulatory molecules in the pathobiological processes that promote and sustain OLP...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28901417/discrimination-of-the-heterogeneity-of-bone-marrow%C3%A2-derived-dendritic-cells
#12
Jing Wang, Xiaomin Dai, Chiaching Hsu, Changsheng Ming, Ying He, Ji Zhang, Lai Wei, Ping Zhou, Cong-Yi Wang, Jun Yang, Nianqiao Gong
The present study aimed to discriminate different subsets of cultured dendritic cells (DCs) to evaluate their immunological characteristics. DCs offer an important foundation for immunological studies, and mouse bone marrow (BM) cells cultured with granulocyte‑macrophage colony‑stimulating factor (GM‑CSF) have been used extensively to generate CD11c+/major histocompatibility complex II+ BM‑derived DCs (BMDCs). Immature DCs are considered to have strong migration and phagocytic antigen‑capturing abilities, whereas mature DCs are thought to activate naive T cells and express high levels of costimulatory cytokines and adhesion molecules...
September 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900681/regulatory-dendritic-cells
#13
Katsuaki Sato, Tomofumi Uto, Tomohiro Fukaya, Hideaki Takagi
Dendritic cells (DCs) comprise heterogeneous subsets, functionally classified into conventional DCs (cDCs) and plasmacytoid DCs (pDCs). DCs are considered to be essential antigen (Ag)-presenting cells (APCs) that play crucial roles in activation and fine-tuning of innate and adaptive immunity under inflammatory conditions, as well as induction of immune tolerance to maintain immune homeostasis under steady-state conditions. Furthermore, DC functions can be modified and influenced by stimulation with various extrinsic factors, such as ligands for pattern-recognition receptors (PRRs) and cytokines...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900679/ctla-4-an-essential-immune-checkpoint-for-t-cell-activation
#14
Shunsuke Chikuma
The response of peripheral T lymphocytes (T cell) is controlled by multiple checkpoints to avoid unwanted activation against self-tissues. Two opposing costimulatory receptors, CD28 and CTLA-4, on T cells bind to the same ligands (CD80 and CD86) on antigen-presenting cells (APCs), and provide positive and negative feedback for T-cell activation, respectively. Early studies suggested that CTLA-4 is induced on activated T cells and binds to CD80/CD86 with much stronger affinity than CD28, providing a competitive inhibition...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900678/socs1-regulator-of-t-cells-in-autoimmunity-and-cancer
#15
Subburaj Ilangumaran, Diwakar Bobbala, Sheela Ramanathan
SOCS1 is a negative feedback regulator of cytokine and growth factor receptor signaling, and plays an indispensable role in attenuating interferon gamma signaling. Studies on SOCS1-deficient mice have established a crucial role for SOCS1 in regulating CD8(+) T cell homeostasis. In the thymus, SOCS1 prevents thymocytes that had failed positive selection from surviving and expanding, ensures negative selection and prevents inappropriate developmental skewing toward the CD8 lineage. In the periphery, SOCS1 not only controls production of T cell stimulatory cytokines but also attenuates the sensitivity of CD8(+) T cells to synergistic cytokine stimulation and antigen non-specific activation...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28895168/9-cis-retinoic-acid-induces-a-distinct-regulatory-dendritic-cell-phenotype-that-modulates-murine-delayed-type-allergy
#16
Lea-Franziska Kraus, Natalie Scheurmann, Denis F Frenzel, Alpaslan Tasdogan, Johannes M Weiss
BACKGROUND: Hand eczema, which is frequently caused by delayed-type allergy, is treated with 9-cis-retinoic acid (9cisRA). However, knowledge on how 9cisRA modulates skin immunity is sparse. OBJECTIVE: As dendritic cells (DCs) are central in the pathogenesis of contact allergy, we investigated 9cisRA modulation of DC function in murine contact hypersensitivity (CHS). METHODS: 9cisRA-differentiated DCs (9cisRA-DCs) were analysed for phenotype and function...
September 12, 2017: Contact Dermatitis
https://www.readbyqxmd.com/read/28878768/natural-igm-and-tlr-agonists-switch-murine-splenic-pan-b-to-regulatory-cells-that-suppress-ischemia-induced-innate-inflammation-via-regulating-nkt-1-cells
#17
Peter I Lobo, Kailo H Schlegel, Amandeep Bajwa, Liping Huang, Mark D Okusa
Natural IgM anti-leukocyte autoantibodies (IgM-ALAs) inhibit inflammation by several mechanisms. Here, we show that pan-B cells and bone marrow-derived dendritic cells (BMDCs) are switched to regulatory cells when pretreated ex vivo with IgM. B cells are also switched to regulatory cells when pretreated ex vivo with CpG but not with LPS. Pre-emptive infusion of such ex vivo induced regulatory cells protects C57BL/6 mice from ischemia-induced acute kidney injury (AKI) via regulation of in vivo NKT-1 cells, which normally amplify the innate inflammatory response to DAMPS released after reperfusion of the ischemic kidney...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878738/overlooked-mechanisms-in-type-1-diabetes-etiology-how-unique-costimulatory-molecules-contribute-to-diabetogenesis
#18
REVIEW
David H Wagner
Type 1 Diabetes (T1D) develops when immune cells invade the pancreatic islets resulting in loss of insulin production in beta cells. T cells have been proven to be central players in that process. What is surprising, however, is that classic mechanisms of tolerance cannot explain diabetogenesis; alternate mechanisms must now be considered. T cell receptor (TCR) revision is the process whereby T cells in the periphery alter TCR expression, outside the safety-net of thymic selection pressures. This process results in an expanded T cell repertoire, capable of responding to a universe of pathogens, but limitations are that increased risk for autoimmune disease development occurs...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28878391/identification-of-a-p53-target-cd137l-that-mediates-growth-suppression-and-immune-response-of-osteosarcoma-cells
#19
Yusuke Tsuda, Chizu Tanikawa, Takafumi Miyamoto, Makoto Hirata, Varalee Yodsurang, Yao-Zhong Zhang, Seiya Imoto, Rui Yamaguchi, Satoru Miyano, Hiroshi Takayanagi, Hirotaka Kawano, Hidewaki Nakagawa, Sakae Tanaka, Koichi Matsuda
p53 encodes a transcription factor that transactivates downstream target genes involved in tumour suppression. Although osteosarcoma frequently has p53 mutations, the role of p53 in osteosarcomagenesis is not fully understood. To explore p53-target genes comprehensively in calvarial bone and find out novel druggable p53 target genes for osteosarcoma, we performed RNA sequencing using the calvarial bone and 23 other tissues from p53 (+/+) and p53 (-/-) mice after radiation exposure. Of 23,813 genes, 69 genes were induced more than two-fold in irradiated p53 (+/+) calvarial bone, and 127 genes were repressed...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28861075/ebola-virus-glycoprotein-induces-an-innate-immune-response-in-vivo-via-tlr4
#20
Chih-Yun Lai, Daniel P Strange, Teri Ann S Wong, Axel T Lehrer, Saguna Verma
Ebola virus (EBOV), a member of the Filoviridae family, causes the most severe form of viral hemorrhagic fever. Although no FDA licensed vaccine or treatment against Ebola virus disease (EVD) is currently available, Ebola virus glycoprotein (GP) is the major antigen used in all candidate Ebola vaccines. Recent reports of protection as quickly as within 6 days of administration of the rVSV-based vaccine expressing EBOV GP before robust humoral responses were generated suggests that the innate immune responses elicited early after vaccination may contribute to the protection...
2017: Frontiers in Microbiology
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