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Immunology Letters

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https://www.readbyqxmd.com/read/29758241/targeting-the-cd73-adenosine-axis-in-immuno-oncology
#1
REVIEW
David Allard, Pavel Chrobak, Bertrand Allard, Nouredin Messaoudi, John Stagg
The ectonucleotidases CD39 and CD73 are cell surface enzymes that catabolize the breakdown of extracellular ATP into adenosine. As such, they constitute critical components of the extracellular purinergic pathway and play important roles in maintaining tissue and immune homeostasis. With the coming of age of cancer immunotherapy, ectonucleotidases and adenosine receptors have emerged as novel therapeutic targets to enhance antitumor immune responses. With early-phase clinical trials showing promising results, it is becoming increasingly important to decipher the distinct mechanisms-of-action of adenosine-targeting agents, identify patients that will benefit from these agents and rationally develop novel synergistic combinations...
May 11, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29715493/spleen-development-is-modulated-by-neonatal-gut-microbiota
#2
M Manuela Rosado, Alaitz Aranburu, Marco Scarsella, Simona Cascioli, Ezio Giorda, Federica Del Chierico, Stefano Levi Mortera, Eva Piano Mortari, Stefania Petrini, Lorenza Putignani, Rita Carsetti
The full development of the mammalian immune system occurs after birth upon exposure to non self-antigens. The gut is the first site of bacterial colonization where it is crucial to create the appropriate microenvironment able to balance effector or tolerogenic responses to external stimuli. It is a well-established fact that at mucosal sites bacteria play a key role in developing the immune system but we ignore how colonising bacteria impact the maturation of the spleen. Here we addressed this issue. Taking advantage of the fact that milk SIgA regulates bacterial colonization of the newborn intestine, we generated immunocompetent mice born either from IgA pro-efficient or IgA deficient females...
April 28, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29709545/dpp9-enzymatic-activity-in-hematopoietic-cells-is-dispensable-for-mouse-hematopoiesis
#3
Munkyung Kim, Lilly von Muenchow, Thomas Le Meur, Benjamin Kueng, Berangere Gapp, Delphine Weber, William Dietrich, Jiri Kovarik, Antonius G Rolink, Iwona Ksiazek
Dipeptidyl peptidase 9 (DPP9) is a ubiquitously expressed intracellular prolyl peptidase implicated in immunoregulation. However, its physiological relevance in the immune system remains largely unknown. We investigated the role of DPP9 enzyme in immune system by characterizing DPP9 knock-in mice expressing a catalytically inactive S729A mutant of DPP9 enzyme (DPP9ki/ki mice). DPP9ki/ki mice show reduced number of lymphoid and myeloid cells in fetal liver and postnatal blood but their hematopoietic cells are fully functional and able to reconstitute lymphoid and myeloid lineages even in competitive mixed chimeras...
April 27, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29709544/identification-and-suppression-of-epidermal-growth-factor-receptor-variant-iii-signaling-in-fibroblast-like-synoviocytes-from-aggressive-rheumatoid-arthritis-by-the-mimotope
#4
Jianying Niu, Changhong Li, Yinji Jin, Rui Xing, Lin Sun, Ruohan Yu, Leilei Jian, Xiangyuan Liu, Lin Yang
Epidermal growth factor receptor (EGFR) signaling has been reported to play a vital role in the pathogenesis of rheumatoid arthritis (RA). In current study, we sought to observe whether the active immunization induced by the mimotope could recognize EGFR, inhibit their signaling and disrupt the pathogenic behavior of fibroblast-like synoviocytes (FLS) from RA patients. We prepared a linked EGFR mimotope and performed series of experiments to detect whether the mimotope could induce the desired immune responses...
April 27, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29702149/the-link-between-bone-microenvironment-and-immune-cells-in-multiple-myeloma-emerging-role-of-cd38
#5
REVIEW
Marina Bolzoni, Denise Toscani, Federica Costa, Emanuela Vicario, Franco Aversa, Nicola Giuliani
The relationship between bone and immune cells is well established both in physiological and pathological conditions. Multiple myeloma (MM) is a plasma cell malignancy characterized by an increase of number and activity of osteoclasts (OCLs) and a decrease of osteoblasts (OBs). These events are responsible for bone lesions of MM patients. OCLs support MM cells survival in vitro and in vivo. Recently, the possible role of OCLs as immunosuppressive cells in the MM BM microenvironment has been underlined. OCLs protect MM cells against T cell-mediated cytotoxicity through the expression of several molecules including programmed death-ligand (PD-L) 1, galectin (Gal) 9, CD200, and indoleamine-2,3-dioxygenase (IDO)...
April 24, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29702148/immunomodulatory-effects-of-cd38-targeting-antibodies
#6
REVIEW
Niels W C J van de Donk
The fist in class CD38-targeting antibody, daratumumab, is currently approved as single agent and in combination with standards of care for the treatment of relapsed and refractory multiple myeloma. Based on the high activity and favorable toxicity profile of daratumumab, other CD38 antibodies, such as isatuximab, MOR202, and TAK-079, are being evaluated in MM and other malignancies. The CD38-targeting antibodies have classic Fc-dependent immune effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC)...
April 24, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29702147/adenosine-signalling-and-the-immune-system-when-a-lot-could-be-too-much
#7
REVIEW
Luca Antonioli, Matteo Fornai, Corrado Blandizzi, Pál Pacher, György Haskó
Adenosine is increasingly recognized as a key mediator of the immune response. Signals delivered by extracellular adenosine are detected and transduced by G-protein-coupled cell-surface receptors, classified into four subtypes: A1 , A2A , A2B and A3 . These receptors, expressed virtually on all immune cells, modulate all aspects of immune/inflammatory responses. These immunoregulatory effects, which are mostly anti-inflammatory, contribute to the general tissue protective effects of adenosine and its receptors...
April 24, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29684393/anti-pseudo-allergy-effect-of-isoliquiritigenin-is-mrgprx2-dependent
#8
Yajing Hou, Delu Che, Pengyu Ma, Tingting Zhao, Yingnan Zeng, Nan Wang
Mast cell (MC) is the key mediate during allergy accours. The classical MC degranulation pathway is mediated by FcεRI aggregation and varies in strength among subjects, whereas a non-classical but analogous pseudo-allergic way was recently reported to occur via MRGPRX2. However, few therapies can directly target pseudo-allergies and related Mrgprs. Isoliquiritigenin (ISL) exerts anti-inflammatory effect in many diseases. In this study, we investigated the anti-pseudo-allergy effects of ISL and its underlying mechanism...
April 20, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29679602/solubility-enhanced-gmyl6-fused-with-a-hexa-lysine-tag-promotes-the-cytotoxicity-of-human-nk-cells
#9
Juanjuan Liu, Yuanyuan Jin, Xiaozhou Feng, Sen Zou, Guangxin Lv, Zhifei Zhang, Zhaoyong Yang
Goat myosin light chain 6 (gMYL6) is a constituent of certain extracted immunization-induced goat anti-cancer bioactive peptides (ACBPs). However, little is known about its activity onto NK cells which are the basic cellular attackers in cancer immunotherapy for patients with malignancies. Because of the complicated extraction process and low yield of gMYL6 out of the goat ACBPs' mixture, the Nano-flow liquid chromatography and C-terminal polycationic tag expression strategy were used to identify and enrich the peptide to investigate its bioactivity against cancers/tumors...
April 18, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29635002/impact-of-antiretroviral-and-tuberculosis-therapies-on-cd4-and-cd8-hiv-m-tuberculosis-specific-t-cell-in-co-infected-subjects
#10
Teresa Chiacchio, Elisa Petruccioli, Valentina Vanini, Gilda Cuzzi, Marco Pio La Manna, Valentina Orlando, Carmela Pinnetti, Alessandro Sampaolesi, Andrea Antinori, Nadia Caccamo, Delia Goletti
BACKGROUND: Human Immunodeficiency Virus (HIV) infection is a risk factor for tuberculosis (TB). Antiretroviral therapy (ART) changed HIV clinical management but it is still unclear how pre-existing HIV/Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cells are restored. AIM: to evaluate the impact of ART and TB therapies on the functional and phenotypic profile of Mtb-specific antigen-response of CD4+ and CD8+ T-cells in prospectively enrolled HIV-TB co-infected patients...
April 7, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29635001/a-new-role-for-mast-cells-as-scavengers-for-clearance-of-erythrocytes-damaged-due-to-oxidative-stress
#11
Priyanka Sharma, Niti Puri
Anemia, inflammation, and oxidative stress are interconnected. Erythrocytes are continuously exposed to oxidative stress, normally and during inflammatory diseases. Systemic mastocytosis and genetic depletion of mast cells affect anemia. In the present study, a direct role for mast cells in clearance of erythrocytes was explored. We show, for the first time, direct phagocytosis of opsonized as well as oxidatively damaged erythrocytes in vitro by mast cell lines, bone marrow derived mast cells (BMMCs) and in vivo by murine peritoneal mast cells...
April 7, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29608924/a20-ameliorates-inflammatory-bowel-disease-in-mice-via-inhibiting-nf-%C3%AE%C2%BAb-and-stat3-activation
#12
Seung Hoon Lee, Hye-Rim Lee, Ji Ye Kwon, KyungAh Jung, Se-Young Kim, Keun-Hyung Cho, JeongWon Choi, Han Hee Lee, Bo-In Lee, Dae-Myung Jue, Mi-La Cho
A20 is a zinc finger protein that effectively inhibits the activation of nuclear factor (NF)-κB to downregulate the expression of tumor necrosis factor-α, interleukin (IL)-1β, and IL-17. A20 also plays a crucial role as a feedback inhibitor of the inflammatory response. Due to its inhibitory role, A20 may be useful in regulating diseases resulting from chronic inflammation and excessive pro-inflammatory cytokine production, such as colitis. Patients with colitis produce high levels of pro-inflammatory cytokines in the intestine...
March 30, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29601942/effects-of-toll-like-receptor-4-on-%C3%AE-2-glycoprotein-i-induced-splenic-t-cell-subsets-differentiation
#13
Chao He, Guiting Zhang, Hong Zhou, Si Cheng, Amel Farwa
Our previous study demonstrated that beta 2-glycoprotein I (β2GPI) stimulation promotes bone marrow derived dendritic cells (BMDCs) maturation and T cell proliferation in a Toll-like receptor 4 (TLR4) dependent manner. However, β2GPI induced T cell differentiation and the role of TLR4 in this process have rarely been reported. In the present study, we focused on the differentiation of splenic T cells in β2GPI immunized Balb/c, C3H/HeN and C3H/HeJ mice. According to our results, Th2 dominated differentiation was observed in β2GPI immunized Balb/c and C3H/HeN mice than in those treated with normal saline (NS), namely the up-regulated levels of Th2 markers GATA3 and IL-4 (p < 0...
March 27, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29601941/different-profile-of-cytokine-production-in-patients-with-systemic-sclerosis-and-association-with-clinical-manifestations
#14
Andréa Tavares Dantas, Anderson Rodrigues de Almeida, Maria Clara Pinheiro Duarte Sampaio, Marina Ferraz Cordeiro, Priscilla Stela Santana de Oliveira, Henrique de Ataíde Mariz, Michelly Cristiny Pereira, Moacyr Jesus Barreto de Melo Rego, Ivan da Rocha Pitta, Angela Luzia Branco Pinto Duarte, Maira Galdino da Rocha Pitta
Immune dysregulation is a central process in the pathogenesis of systemic sclerosis (SSc). Cytokines produced by lymphocytes and monocytes are important mediators and induce tissue damage, recruit additional inflammatory cells, and promote extracellular matrix production and fibrosis. In the present research, we aimed to study the associations between levels of cytokines in serum and culture supernatants from peripheral blood mononuclear cells (PBMCs) and clinical manifestations in SSc patients. Serum samples were obtained from 56 SSc patients and 56 unrelated age- and gender-matched healthy individuals...
March 27, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29601940/novel-intranasal-pertussis-vaccine-based-on-bacterium-like-particles-as-a-mucosal-adjuvant
#15
Wei Shi, Yiming Kou, Hao Jiang, Feng Gao, Wei Kong, Weiheng Su, Fei Xu, Chunlai Jiang
Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination. The development of a novel pertussis vaccine, especially an intranasal (i.n.) vaccine is undoubtedly necessary, and mucosal adjuvants have been explored to enhance the immune response. In the present study, bacterium-like particles (BLPs) were adopted as a mucosal adjuvant for an i.n. pertussis vaccine and evaluated on the ability to induce serum and mucosal antibodies as well as potency against i...
March 27, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29601939/dec1-stra13-is-a-key-negative-regulator-of-activation-induced-proliferation-of-human-b-cells-highly-expressed-in-anergic-cells
#16
Alessandro Camponeschi, Laura Todi, Cristina Cristofoletti, Cristina Lazzeri, Maurizio Carbonari, Milica Mitrevski, Ramona Marrapodi, Martina Del Padre, Massimo Fiorilli, Milvia Casato, Marcella Visentini
The transcription factor DEC1/STRA13 (also known as BHLHE40 and SHARP2) is involved in a number of processes including inhibition of cell proliferation and delay of cell cycle, and is a negative regulator of B cell activation and development in mice. We show here that, unlike in mice, DEC1/STRA13 expression is induced in human naïve and memory resting B cells by activation through the B-cell receptor (BCR) or Toll-like receptor 9 (TLR9). siRNA silencing of DEC1/STRA13 increases the capacity of activated B cells to perform a high number of divisions after TLR9 ligation...
March 27, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29601938/gene-silencing-of-znt8-attenuates-inflammation-and-protects-pancreatic-tissue-injury-in-t1d
#17
Hong Sun, Cunyu Li, Shufa Li, Xunhua Li, Jinguang Wang, Zhongqi Zhou, Mingtao Shao
T lymphocyte mediated inflammation contributes to the development of T1D. Zinc Transporter 8 (ZnT8) has emerged as a target of autoreactive T cells in human T1D in recent years. However, the regulating of ZnT8 in T1D has not been identified. We make a hypothesis that whether alternation of ZnT8 level could attenuate inflammation and protect pancreatic tissue injury in T1D. In this study, we utilized ZnT8 shRNA to inhibit ZnT8 expression, and detected inflammation, glucose tolerance and pancreatic tissue of NOD mice...
March 27, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29581081/silencing-socs1-in-dendritic-cells-promote-survival-of-mice-with-systemic-candida-albicans-infection-via-inducing-th1-cell-differentiation
#18
Dongmei Shi, Dongmei Li, Qiong Wang, Xue Kong, Huan Mei, Yongnian Shen, Weida Liu
Enhancing the immunity conferred by dendritic cells (DCs) to fungal infection represents a promising strategy in the number of immunocompromised individuals. In a previous study, we demonstrated that suppressor of cytokine signaling 1 (SOCS1) silencing can promote the maturation of DCs and induce an immune response against Candida albicans (C. albicans) in vitro. Herein, the effectiveness of SOCS1 suppression administered by SOCS1-siRNA-treated DCs is further evaluated in systemic candidiasis mouse model. The SOCS1-silenced DCs increase mouse survival and significantly decrease fungal colonization in the kidneys...
March 23, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29571741/immunobiologically-relevant-level-of-aflatoxin-b-1-alters-transcription-of-key-functional-immune-genes-phagocytosis-and-survival-of-human-dendritic-cells
#19
Jalil Mehrzad, Abbas Bahari, Mohammad Reza Bassami, Mahmoud Mahmoudi, Hesam Dehghani
The effects of naturally occurring levels of aflatoxin (AF) B1 on the expression of key molecules and function of dendritic cells (DCs) were investigated on human monocyte-derived DCs (MDDCs) by cell culture, RT-qPCR, and flow cytometry. An environmentally relevant level of AFB1 remarkably impaired the phagocytic capacity of MDDCs. Furthermore, AFB1 significantly affected the transcript levels of some key functional genes in MDDCs. It caused an up-regulation of key transcripts in cytochrome P450 (CYP) family, MyD88, NF-KB, TNF-α, TLR2, TLR4, COX-2, HLA-DR, CCR7, CD209, LFA3 and CD16...
March 20, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29550257/canonical-and-non-canonical-adenosinergic-pathways
#20
REVIEW
E Ferretti, A L Horenstein, C Canzonetta, F Costa, F Morandi
Adenosine (ADO) is an immunosuppressive molecule with multiple functions in different human organs. ADO is released through the concerted action of surface molecules endowed with enzymatic functions, that belong to two different adenosinergic pathways. The canonical pathway is started by CD39, that converts ATP to AMP. On the other hand, the non-canonical pathway metabolizes NAD+ to ADPR, through the action of CD38. The latter byproduct is then converted to AMP by CD203a/PC-1. Both pathways converge to CD73, that fully degrades AMP to the final product ADO...
March 14, 2018: Immunology Letters
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