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Alok K Verma, Hemanth K Kandikattu, Murli Manohar, Anshi Shukla, Sathisha Upparahalli Venkateshaiah, Xiang Zhu, Anil Mishra
Baseline eosinophils reside in the gastrointestinal tract; however, in several allergic disorders, excessive eosinophils accumulate in the blood as well in the tissues. Recently, we showed in vitro that interleukin (IL)-18 matures and transforms IL-5 generated eosinophils into the pathogenic eosinophils that are detected in human allergic diseases. To examine the role of local induction of IL-18 in promoting eosinophil-associated intestinal disorders. We generated enterocyte IL-18 overexpressing mice using the rat intestinal fatty acid-binding promoter (Fabpi) and analyzed tissue IL-18 overexpression and eosinophilia by performing real-time PCR, ELISA, and anti-MBP immunostaining...
February 19, 2019: Immunology
Sarah S Geiger, Annie M Curtis, Luke A J O'Neill, Richard M Siegel
Innate immune responses vary in a circadian manner, and more recent investigations aim to understand the underlying molecular mechanisms. Cytokine production varies significantly over the course of a day depending on the time of stimulation by pathogens or Toll-Like Receptor ligands, and multiple signalling pathways linked to the cell-autonomous circadian clock modulate innate immunity. Recognition of foreign material, especially by innate immune cells, engages a myriad of receptors which trigger inflammatory responses, as well as endocytosis and degradation and/or processing for antigen presentation...
February 18, 2019: Immunology
Richard K Tennant, Barbara Holzer, John Love, Elma Tchilian, Harry N White
Designing improved vaccines against mutable viruses such as Dengue and Influenza would be helped by a better understanding of how the B-cell memory compartment responds to variant antigens. Towards this we have recently shown after secondary immunization of mice with a widely variant Dengue envelope protein, with only 63% amino-acid identity, that IgM+ memory B-cells with few mutations supported an efficient secondary germinal centre (GC) and serum response, superior to a primary response to the same protein...
February 15, 2019: Immunology
Radhika Gudi, Nicolas Perez, Benjamin M Johnson, M Hanief Sofi, Robert Brown, Songhua Quan, Subha Karumuthil-Melethil, Chenthamarakshan Vasu
Since the dietary supplement and prebiotic value of β-glucan-rich products have been widely recognized and the dietary approaches for modulating autoimmunity have been increasingly explored, we assessed the impact of oral administration of high-pure yeast β-glucan (YBG) on gut immune function, microbiota and type 1 diabetes (T1D) using mouse models. Oral administration of this non-digestible complex polysaccharide caused a Dectin-1-dependent immune response involving increased expression of IL10, retinaldehyde dehydrogenase (Raldh) and pro-inflammatory cytokines in the gut mucosa...
February 3, 2019: Immunology
Francisco E Velázquez, Marina Anastasiou, Francisco J Carrillo-Salinas, Njabulo Ngwenyama, Ane M Salvador, Tania Nevers, Pilar Alcaide
T helper type 17 lymphocytes (Th17 cells) infiltrate the central nervous system (CNS), induce inflammation and demyelination and play a pivotal role in the pathogenesis of multiple sclerosis (MS). Sialomucin CD43 is highly expressed in Th17 cells and mediates adhesion to endothelial selectin (E-selectin), an initiating step in Th17 cell recruitment to sites of inflammation. CD43-/- mice have impaired Th17 cell recruitment to the CNS and are protected from Experimental Autoimmune Encephalomyelitis (EAE), the mouse model of multiple sclerosis...
January 28, 2019: Immunology
Junfeng Zhang, Yunsheng Zhang, Qingpeng Wang, Chunlei Li, Hongxin Deng, Chuanping Si, Huabao Xiong
Interleukin 35 (IL-35) is a recently identified heterodimeric cytokine in the IL-12 family. It consists of an IL-12 subunit α chain (P35) and IL-27 subunit Epstein-Barr virus-induced gene 3 (EBI3) β chain. Unlike the other IL-12 family members, it signals through four unconventional receptors: IL-12Rβ2-IL-27Rα, IL-12Rβ2-IL-12Rβ2, IL-12Rβ2-GP130, and GP130-GP130. IL-35 signaling is mainly carried out via the signal transducer and activator of transcription (STAT) family of proteins. It is secreted not only by regulatory T cells (Tregs), but also by CD8+ Tregs, activated dendritic cells, and regulatory B cells...
January 25, 2019: Immunology
Lei Yang, Liqun Tu, Peiyan Zhao, Ying Wang, Shengnan Wang, Wenting Lu, Yangyang Wang, Xin Li, Yongli Yu, Shucheng Hua, Liying Wang
The excessive activation of interferon regulatory factor 7 (IRF7) promotes the development of acute lung injury (ALI) caused by influenza A virus (IAV). However, the deficiency of IRF7 increases the susceptibility to deadly IAV infection in both human and mice. To test whether the attenuation rather than the abolishment of IRF7 activity in local infectious sites could alleviate IAV-induced ALI, we established IAV-infected mouse model and trachea/lung tissue culture systems, and designed two IRF7-interfering oligodeoxynucleotides (IRF7-rODNs), IRF7-rODN M1 and IRF7-rODN A1, based on the mouse and human consensus sequences of IRF7 binding sites of Ifna/IFNA genes, respectively...
January 22, 2019: Immunology
Sarang Tartey, Thirumala-Devi Kanneganti
Dysregulated inflammation is one of the hallmarks of cancer initiation and progression. Emerging evidence indicates that inflammasomes play a central role in regulating immune cell functions in various infections and cancer. Inflammasomes are multimeric complexes consisting of nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). Among the NLRs, NOD1, NOD2, and NLRP3 respond to a variety of endogenous (i.e., damage-associated molecular patterns) and exogenous (i.e., pathogen-associated molecular patterns) stimuli...
January 21, 2019: Immunology
Shamik Majumdar, Vasista Adiga, Abinaya Raghavan, Supriya Rajendra Rananaware, Dipankar Nandi
The development of immunocompetent T cells entails a complex pathway of differentiation in the thymus. Thymic atrophy occurs with ageing and during conditions such as malnutrition, infections, cancer chemotherapy etc. The comparative changes in thymic subsets under different modes of thymic atrophy and the mechanisms involved are not well characterized. These aspects were investigated, using mice infected with Salmonella Typhimurium, injection with lipopolysaccharide (LPS), an inflammatory but non-infectious stimulus, Etoposide (Eto), a drug used to treat some cancers, and Dexamethasone (Dex), a steroid which is used to lower some inflammatory diseases...
January 19, 2019: Immunology
Jin-Sil Park, Si-Young Choi, Sun-Hee Hwang, Sung-Min Kim, JeongWon Choi, Kyung-Ah Jung, Ji Ye Kwon, Young-Yun Kong, Mi-La Cho, Sung-Hwan Park
CR6-interacting factor 1 (CRIF1) is a nuclear protein that interacts with other nuclear factors and androgen receptors, and is implicated in the regulation of cell cycle progression and cell growth. In this study, we examined whether Crif1 exerts an immunoregulatory effect by modulating the differentiation and function of pathogenic T cells. To this end, the role of CRIF1 in rheumatoid arthritis (RA), a systemic autoimmune disease characterized by hyperplasia of synovial tissue and progressive destruction of articular cartilage structure by pathogenic immune cells (such as Th17 cells), was investigated...
December 26, 2018: Immunology
Yingjiao Cao, Yumei He, Xiangyang Wang, Yongdong Liu, Kun Shi, Zheng Zheng, Xue Su, Aihua Lei, Juan He, Jie Zhou
Hyperactivation of the type 2 immune response is the major mechanism of allergic asthma, in which both group 2 innate lymphoid cells (ILC2s) and type 2 helper T (Th2) cells participate. Myeloid-derived suppressor cells (MDSCs) alleviate asthma by suppressing Th2 cells. However, the potential effects of MDSCs on the biological functions of ILC2s remain largely unknown. Here, we examined the roles of MDSCs (MDSCs) in the modulation of ILC2 function. Our results showed that polymorphonuclear (PMN)-MDSCs, but not monocytic (M-) MDSCs, effectively suppressed the cytokine production of ILC2s both in vitro and in vivo, thereby alleviating airway inflammation...
December 21, 2018: Immunology
Leidy Y Bastidas-Legarda, Salim I Khakoo
Natural Killer (NK) cells are lymphocytes of the innate immune system with essential roles during viral infections. NK cell functions are mediated through a repertoire of non-rearranging inhibitory and activating receptors that interact with MHC:peptide complexes on the surface of infected cells. Recent work studying the conserved CD94:NKG2A and variable KIR:MHC systems suggest that these two receptor families may have subtly different properties in terms of interactions with MHC class I bound peptides, and in recognition of down-regulation of MHC class I...
December 20, 2018: Immunology
Maran L Sprouse, Nicholas A Bates, Krysta M Felix, Hsin-Jung Joyce Wu
The immune system is essential for maintaining a delicate balance between eliminating pathogens and maintaining tolerance to self-tissues to avoid autoimmunity. An enormous and complex community of gut microbiota provides essential health benefits to the host, particularly by regulating immune homeostasis. Many of the metabolites derived from commensals can impact host health by directly regulating the immune system. Many autoimmune diseases arise from an imbalance between pathogenic effector T cells and regulatory T (Tregs) cells...
December 17, 2018: Immunology
Renu Balyan, Rupali Gund, Amanpreet Singh Chawla, Satyajeet P Khare, Saurabh J Pradhan, Sanket Rane, Sanjeev Galande, Jeannine Marie Durdik, Anna George, Vineeta Bal, Satyajit Rath
We have previously demonstrated co-receptor level-associated functional heterogeneity in apparently homogenous naive peripheral CD4 T cells, dependent on MHC-mediated tonic signals. Since maturation pathways can differ between naive CD4 and naive CD8 cells, we tested whether the latter showed similar co-receptor level-associated functional heterogeneity. We report that, when either polyclonal and TCR-transgenic monoclonal peripheral naive CD8 T cells from young mice were separated into CD8hi and CD8lo subsets, CD8lo cells responded poorly, but CD8hi and CD8lo subsets of CD8 single-positive (SP) thymocytes responded similarly...
December 17, 2018: Immunology
Nina Sopel, Julia Koelle, Sonja Dumendiak, Sonja Koch, Martin Reichel, Cosima Rhein, Johannes Kornhuber, Susetta Finotto
Acid sphingomyelinase is one of the enzymes that catalyzes the breakdown of sphingomyelin to ceramide and phosphorylcholine. In this study, we aimed at elucidating the role of ASM in allergic asthma. We used an Ovalbumin-induced murine model of asthma where we compared wild type and ASM-deficient mice. In wild type mice, S-ASM activity in the bronchoalveolar lavage fluid (BALF) was found increased in the acute OVA-model, but not in a tolerogenic model. Furthermore, in the absence of ASM, the serum IgE level was found reduced, as compared to wild type mice, while an accumulation of interstitial macrophages and foreign antigen induced T regulatory cells along with exhausted CD4+ PD1+ T cells was observed in the lungs of ASM-/- mice...
December 16, 2018: Immunology
Claire E Macdougall, M Paula Longhi
Healthy white adipose tissue (WAT) participates in regulating systemic metabolism, whilst dysfunctional WAT plays a prominent role in the development of obesity-associated comorbidities. Tissue resident immune cells are important for maintaining WAT homeostasis, including conventional dendritic cells (cDCs) which are critical in the initiation and regulation of adaptive immune responses. Due to phenotypic overlap with other myeloid cells, the distinct contribution of WAT cDCs has been poorly understood. This review will discuss the contribution of cDCs in the maintenance of WAT homeostasis...
December 15, 2018: Immunology
Nital Sumaria, Stefania Martin, Daniel J Pennington
Murine γδ T cells display diverse responses to pathogens and tumours through early provision of pro-inflammatory cytokines such as interleukin-17A (IL-17) and interferon-γ (IFNγ). Although it is now clear that acquisition of these cytokine-secreting effector fates is to a great extent developmentally pre-programmed in the thymus, the stages through which γδ progenitor cells transition, and the underlying mechanistic processes that govern these commitment events, are still largely unclear. Here, we review recent progress in the field, with particular consideration to how TCRγδ signalling impacts on developmental programs initiated prior to TCRγδ expression...
December 15, 2018: Immunology
Takamasa Kido, Kenji Ishiwata, Machi Suka, Hiroyuki Yanagisawa
Nutritional zinc deficiency leads to immune dysfunction and aggravates inflammation. However, the underlying mechanism remains unknown. In this study, the relationship between macrophage subtypes (M1 and M2) or helper T lymphocytes (Th1 and Th2) were investigated using the spleen from rats fed zinc-deficient or standard diet. In experiment I, five-week-old male Sprague-Dawley rats were fed zinc-deficient diet (without zinc additives) or standard diet (containing 0.01% zinc) for 6 weeks. In experiment II, the rats were divided into four groups: one group was fed a standard diet for 6 weeks; two groups were fed zinc-deficient diet and were injected three times a week with either saline or interleukin (IL)-4 (zinc-deficient/IL-4 i...
December 15, 2018: Immunology
Leonie Unterholzner, Jessica F Almine
Intracellular DNA and RNA sensors play a vital part in the innate immune response to viruses and other intracellular pathogens, causing the secretion of type I interferons, cytokines and chemokines from infected cells. Pathogen RNA can be detected by RIG-I-like receptors in the cytosol, while cytosolic DNA is recognised by DNA sensors such as cyclic GMP-AMP synthase (cGAS). The resulting local immune response, which is initiated within hours of infection, is able to eliminate many pathogens before they are able to establish an infection in the host...
November 30, 2018: Immunology
Rachel Wong, Deepta Bhattacharya
The production of pathogen-specific B cells and antibodies underlies protective immunity elicited by most vaccines and many infections. Humoral immunity follows a regulated process by which high-affinity antibody-secreting plasma cells and memory B cells are generated. Yet for certain pathogens, protective immunity is inefficiently generated and/or maintained. For example, Dengue virus infections lead to lasting immunity against re-infection by the same serotype. However, if infected with a different Dengue serotype, the individual is predisposed to more severe disease than if he/she was completely naive...
November 29, 2018: Immunology
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