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Parvaneh Mehrbod, Muna Ali Abdalla, Fatemeh Fotouhi, Masoumeh Heidarzadeh, Abimbola O Aro, Jacobus N Eloff, Lyndy J McGaw, Folorunso O Fasina
BACKGROUND: Influenza infection is a major public health threat. The role of influenza A virus-induced inflammatory response in severe cases of this disease is widely recognized. Drug resistance and side effects of chemical treatments have been observed, resulting in increased interest in alternative use of herbal medications for prophylaxis against this infection. The South African medicinal plant, Rapanea melanophloeos (RM) (L.) Mez of the family Myrsinaceae was selected owing to its traditional use for the treatment of several diseases such as respiratory ailments and also previous preliminary studies of anti-influenza activity of its methanolic extract...
June 15, 2018: BMC Complementary and Alternative Medicine
Norio Chihara, Asaf Madi, Takaaki Kondo, Huiyuan Zhang, Nandini Acharya, Meromit Singer, Jackson Nyman, Nemanja D Marjanovic, Monika S Kowalczyk, Chao Wang, Sema Kurtulus, Travis Law, Yasaman Etminan, James Nevin, Christopher D Buckley, Patrick R Burkett, Jason D Buenrostro, Orit Rozenblatt-Rosen, Ana C Anderson, Aviv Regev, Vijay K Kuchroo
The expression of co-inhibitory receptors, such as CTLA-4 and PD-1, on effector T cells is a key mechanism for ensuring immune homeostasis. Dysregulated expression of co-inhibitory receptors on CD4+ T cells promotes autoimmunity, whereas sustained overexpression on CD8+ T cells promotes T cell dysfunction or exhaustion, leading to impaired ability to clear chronic viral infections and diseases such as cancer1,2 . Here, using RNA and protein expression profiling at single-cell resolution in mouse cells, we identify a module of co-inhibitory receptors that includes not only several known co-inhibitory receptors (PD-1, TIM-3, LAG-3 and TIGIT) but also many new surface receptors...
June 13, 2018: Nature
Xiu-Zhi Wu, Xin-Yu Shi, Kan Zhai, Feng-Shuang Yi, Zhen Wang, Wen Wang, Xue-Bin Pei, Li-Li Xu, Zheng Wang, Huan-Zhong Shi
Inflammatory signaling networks between tumor cells and immune cells contribute to the development of malignant pleural effusion (MPE). B cells have been found in MPE, however, little is known about their roles there. In the present study, by using mouse MPE models, we noted that although the total B cells in MPE were decreased as compared to the corresponding blood and spleen, the percentage of activated naïve B cells expressing higher levels of CD80, CD86, MHC-II, CD44, CD69, and PD-L1 molecules were increased in wild type mouse MPE...
May 31, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Nicholas J Bernard
No abstract text is available yet for this article.
May 25, 2018: Nature Reviews. Rheumatology
Christoph Nowak, Axel C Carlsson, Carl Johan Östgren, Fredrik H Nyström, Moudud Alam, Tobias Feldreich, Johan Sundström, Juan-Jesus Carrero, Jerzy Leppert, Pär Hedberg, Egil Henriksen, Antonio C Cordeiro, Vilmantas Giedraitis, Lars Lind, Erik Ingelsson, Tove Fall, Johan Ärnlöv
AIMS/HYPOTHESIS: Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. METHODS: We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay...
May 24, 2018: Diabetologia
Aiysha Thompson, Selinda J Orr
Invasive fungal infections cause approximately 1.5 million deaths per year worldwide and are a growing threat to human health. Current anti-fungal therapies are often insufficient, therefore studies into host-pathogen interactions are critical for the development of novel therapies to improve mortality rates. Myeloid cells, such as macrophages and dendritic cells, express pattern recognition receptor (PRRs), which are important for fungal recognition. Engagement of these PRRs by fungal pathogens induces multiple cytokines, which in turn activate T effector responses...
May 21, 2018: Cytokine
Xinxin Tong, Shengjie Chen, Huanqin Zheng, Shiguang Huang, Fangli Lu
Interleukin 27 (IL-27) is a member of the IL-6/IL-12 family, and IL-27 receptor (IL-27R) consists of WSX-1 (the IL-27Rα subunit) and the signal-transducing subunit gp130. Human and mouse mast cells (MCs) express the IL-27R. To explore the expressions of IL-27/IL-27R subunits (WSX-1 and gp130) during acute ocular toxoplasmosis (OT), we established mouse model by intraocular injection of 500 Toxoplasma gondii RH strain tachyzoites. Histopathological changes were analyzed, MCs were counted by toluidine blue staining, and tryptase+ /IL-27+ MCs were examined by immunofluorescence double-staining in the eyes and cervical lymph nodes (CLNs) of T...
May 19, 2018: Parasitology Research
Kristian Holz, Marco Prinz, Stefanie M Brendecke, Alexandra Hölscher, Fengyuan Deng, Hans-Willi Mitrücker, Stefan Rose-John, Christoph Hölscher
gp130 cytokines are differentially involved in regulating the T helper (H) 17-driven pathogenesis of experimental autoimmune encephalomyelitis (EAE), the animal model of human multiple sclerosis. Interleukin (IL)-6 directly promotes the development of TH17 cells through the gp130/IL-6R complex. By contrast, IL-27 has been shown to suppress a TH17 immune response by gp130/IL-27R-alpha (α) receptor ligation. The IL-27-dependent regulation of a TH17 development could be mediated on the level of CD4 T cells. However, because IL-27 also suppresses the secretion of the TH17-driving cytokines IL-6 and IL-12/23p40 in accessory cells, TH17 immune responses may also be controlled by IL-27 on the level of macrophages and/or neutrophils...
2018: Frontiers in Immunology
Laura Bouchareychas, Eva M Grössinger, Mincheol Kang, Iannis E Adamopoulos
γδ T cells have been implicated in inflammatory diseases as an important link between the innate and adaptive immune responses, however, their role in inflammatory arthritis remain unclear. To define the contribution of γδ T cells in the pathogenesis of inflammatory arthritis, we performed gene transfer of IL-23 in B10.RIII mice to establish joint inflammation in the presence or absence of γδ T cells. We demonstrated that γδ T cell blockade has a protective effect on arthritis incidence and severity by preventing neutrophil accumulation in the blood, spleen and bone marrow as well as by reducing neutrophil infiltration into the joints...
May 15, 2018: Scientific Reports
Fang Xu, Shihui Lin, Xingxing Yan, Chuanjiang Wang, Hongmei Tu, Yibing Yin, Ju Cao
Background: IL-38 is the most recently characterized cytokine of the IL-1 family. However, its role in sepsis remains unknown. Methods: Circulating IL-38 was measured in two cohorts of adult and pediatric patients with sepsis. Using two murine models of lipopolysaccharide (LPS)-induced endotoxinemia and cecal ligation and puncture (CLP)-induced sepsis, the effects of IL-38 on survival, inflammation, tissue injury, or bacterial clearance were assessed. Results: Serum IL-38 concentrations were significantly elevated in adult and pediatric patients with sepsis relative to corresponding healthy adult and pediatric controls, respectively...
May 12, 2018: Journal of Infectious Diseases
Yu Chen, Rui Zhang, Linjun Zeng, Hong Wei, Yang Chen, Jianhui Zeng
AIM: Accumulating data showed that IL-27 polymorphisms are linked to the susceptibility of some autoimmune diseases. We assessed whether there was an association between two single nucleotide polymorphisms (SNPs) of IL-27 gene and dilated cardiomyopathy (DCM). MATERIALS & METHODS: Two SNPs (rs153109 and rs17855750) of IL-27 gene were genotyped by PCR-restriction fragment length polymorphism in 261 DCM patients and 303 unrelated healthy subjects in Chinese Han population...
September 2017: Personalized Medicine
Li Bai, Huihui Fang, Sisi Xia, Ruochan Zhang, Liwu Li, Jordi Ochando, Jiangnan Xu, Yaozhong Ding
IL-22 plays an important role in tissue repair and inflammatory responses, and is implicated in the pathogenesis of psoriasis, ulcerative colitis, as well as liver and pancreas damage. The molecular mechanisms of its regulation have been actively studied. Here, we show that the differential regulation of IL-22 expression in CD4+ T cells by IL-6 and IL-27 was detected rapidly after stimulation. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays demonstrated that both STAT1 and STAT3 directly bind to the STAT responsive elements (SRE) of the IL-22 promoter, and the balance between activated STAT3 and STAT1 determines IL-22 promoter activities...
May 8, 2018: Biochemical and Biophysical Research Communications
Lazaros I Sakkas, Athanasios Mavropoulos, Carlo Perricone, Dimitrios P Bogdanos
IL-35 is a relatively new cytokine that emerges as an important immunomodulator. IL-35 belongs to IL-12 cytokine family that includes IL-12, IL-23, IL-27, and IL-35. These cytokines are heterodimers that share subunits and their receptors also share subunits. Whereas IL-12 and IL-23 are clearly proinflammatory cytokines, the role of IL-35 is less clear. In mice, IL-35 appears to be anti-inflammatory and to protect from autoimmune inflammatory diseases. IL-35 induces the expansion of a subset of regulatory T cells (Tregs) and Bregs and mediates their suppressive function and inhibits Th17 cells...
May 11, 2018: Immunologic Research
Jianmin Zhu, Jin-Qing Liu, Zhihao Liu, Lisha Wu, Min Shi, Jianchao Zhang, Jonathan P Davis, Xue-Feng Bai
Interleukin-27 (IL-27) and its subunit P28 (also known as IL-30) have been shown to inhibit autoimmunity and have been suggested as potential immunotherapeutic for autoimmune diseases such as multiple sclerosis (MS). However, the potential of IL-27 and IL-30 as immunotherapeutic, and their mechanisms of action have not been fully understood. In this study, we evaluated the efficacy of adeno-associated viral vector (AAV)-delivered IL-27 (AAV-IL-27) and IL-30 (AAV-IL-30) in a murine model of MS. We found that one single administration of AAV-IL-27, but not AAV-IL-30 completely blocked the development of experimental autoimmune encephalomyelitis (EAE)...
2018: Frontiers in Immunology
Hanna Erdmann, Jochen Behrends, Kristina Ritter, Alexandra Hölscher, Johanna Volz, Ida Rosenkrands, Christoph Hölscher
During Mycobacterium tuberculosis (Mtb) infection, mice lacking the IL-27R exhibit lower bacterial burdens but develop an immunopathological sequelae in comparison to wild-type mice. We here show that this phenotype correlates with an enhanced recruitment of antigen-specific CCR6+ CD4+ T cells and an increased frequency of IL-17A-producing CD4+ T cells. By comparing the outcome of Mtb infection in C57BL/6, IL-27R-deficient and IL-27R/IL-17A-double deficient mice, we observed that both the increased protection and elevated immunopathology are supported by IL-17A...
May 4, 2018: Mucosal Immunology
Naoko Orii, Izuru Mizoguchi, Yukino Chiba, Hideaki Hasegawa, Mio Ohashi, Mingli Xu, Taro Nagai, Nakaba Ochiai, Yuki Mochizuki, Toshiyuki Owaki, Takayuki Yoshimoto
Interleukin (IL)-27 is a multifunctional cytokine that belongs to the IL-6/IL-12 family and has potent antitumor activity through various mechanisms. Our novel findings indicate that IL-27 directly acts on hematopoietic stem cells and promotes their expansion and differentiation into myeloid progenitors to control infection and to eradicate tumors.
2018: Oncoimmunology
Heeju Ryu, Hoyong Lim, Garam Choi, Young-Jun Park, Minkyoung Cho, Hyeongjin Na, Chul Won Ahn, Young Chul Kim, Wan-Uk Kim, Sang-Hak Lee, Yeonseok Chung
The incidence of atherosclerosis is higher among patients with systemic lupus erythematosus (SLE); however, the mechanism by which an atherogenic environment affects autoimmunity remains unclear. We found that reconstitution of atherosclerosis-prone Apoe-/- and Ldlr-/- mice with bone marrow from lupus-prone BXD2 mice resulted in increased autoantibody production and glomerulonephritis. This enhanced disease was associated with an increase in CXCR3+ follicular helper T cells (TFH cells). TFH cells isolated from Apoe-/- mice had higher expression of genes associated with inflammatory responses and SLE and were more potent in inducing production of the immunoglobulin IgG2c...
April 30, 2018: Nature Immunology
Yue He, Chaokui Wang, Guannan Su, Bolin Deng, Zi Ye, Yang Huang, Gangxiang Yuan, Kijlstra Aize, Hong Li, Peizeng Yang
PURPOSE: A20 is a ubiquitously expressed and inducible cytosolic protein, which plays an important role in the negative regulation of inflammation and immunity. In this study, we investigated the role of A20 in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) disease. METHODS: The levels of A20 in peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) were detected in BD patients with active and inactive uveitis, VKH patients with active and inactive uveitis, and normal subjects, respectively, by real-time PCR...
April 26, 2018: British Journal of Ophthalmology
Mathis Düster, Martina Becker, Ann-Christin Gnirck, Malte Wunderlich, Ulf Panzer, Jan-Eric Turner
Innate lymphoid cells (ILCs) are important regulators of the immune response and play a crucial role in the restoration of tissue homeostasis after injury. GATA-3+ IL-13- and IL-5-producing group 2 innate lymphoid cells (ILC2s) have been shown to promote tissue repair in barrier organs, but despite extensive research on ILCs in the recent years, their potential role in autoimmune diseases is still incompletely understood. In the present study, we investigate the role of ILC2s in the MRL/MpJ-Faslpr (MRL-lpr) mouse model for severe organ manifestation of systemic lupus erythematosus (SLE)...
April 19, 2018: European Journal of Immunology
Jianmin Zhu, Jin-Qing Liu, Min Shi, Xinhua Cheng, Miao Ding, Jianchao C Zhang, Jonathan P Davis, Sanjay Varikuti, Abhay R Satoskar, Lanchun Lu, Xueliang Pan, Pan Zheng, Yang Liu, Xue-Feng Bai
Tumor-induced expansion of Tregs is a significant obstacle to cancer immunotherapy. However, traditional approaches to deplete Tregs are often inefficient, provoking autoimmunity. We show here that administration of IL-27-expressing recombinant adeno-associated virus (AAV-IL-27) significantly inhibits tumor growth and enhances T cell responses in tumors. Strikingly, we found that AAV-IL-27 treatment causes rapid depletion of Tregs in peripheral blood, lymphoid organs, and - most pronouncedly - tumor microenvironment...
April 5, 2018: JCI Insight
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