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Immune dysregulation

Jürgen Maibaum, Sha-Mei Liao, Anna Vulpetti, Nils Ostermann, Stefan Randl, Simon Rüdisser, Edwige Lorthiois, Paul Erbel, Bernd Kinzel, Fabrice A Kolb, Samuel Barbieri, Julia Wagner, Corinne Durand, Kamal Fettis, Solene Dussauge, Nicola Hughes, Omar Delgado, Ulrich Hommel, Ty Gould, Aengus Mac Sweeney, Bernd Gerhartz, Frederic Cumin, Stefanie Flohr, Anna Schubart, Bruce Jaffee, Richard Harrison, Antonio Maria Risitano, Jörg Eder, Karen Anderson
Complement is a key component of the innate immune system, recognizing pathogens and promoting their elimination. Complement component 3 (C3) is the central component of the system. Activation of C3 can be initiated by three distinct routes-the classical, the lectin and the alternative pathways-with the alternative pathway also acting as an amplification loop for the other two pathways. The protease factor D (FD) is essential for this amplification process, which, when dysregulated, predisposes individuals to diverse disorders including age-related macular degeneration and paroxysmal nocturnal hemoglobinuria (PNH)...
October 24, 2016: Nature Chemical Biology
Bethany L Mundy-Bosse, Steven D Scoville, Li Chen, Kathleen McConnell, Hsiaoyin C Mao, Elshafa H Ahmed, Nicholas Zorko, Sophia Harvey, Jordan Cole, Xiaoli Zhang, Stefan Costinean, Carlo M Croce, Karilyn Larkin, John C Byrd, Sumithira Vasu, William Blum, Jianhua Yu, Aharon G Freud, Michael A Caligiuri
Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell-depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients...
October 24, 2016: Journal of Clinical Investigation
José Peña, Haiyin Chen-Harris, Jonathan E Allen, Mona Hwang, Maher Elsheikh, Shalini Mabery, Helle Bielefeldt-Ohmann, Adam T Zemla, Richard A Bowen, Monica K Borucki
In vivo serial passage of non-pathogenic viruses has been shown to lead to increased viral virulence, and although the precise mechanism(s) are not clear, it is known that both host and viral factors are associated with increased pathogenicity. Under- or overnutrition leads to a decreased or dysregulated immune response and can increase viral mutant spectrum diversity and virulence. The objective of this study was to identify the role of viral mutant spectra dynamics and host immunocompetence in the development of pathogenicity during in vivo passage...
January 2016: Virus Evolution
Helen E Vuong, Elaine Y Hsiao
Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder that affects one in 45 children in the United States, with a similarly striking prevalence in countries around the world. However, mechanisms underlying its etiology and manifestations remain poorly understood. Although ASD is diagnosed based on the presence and severity of impaired social communication and repetitive behavior, immune dysregulation and gastrointestinal issues are common comorbidities. The microbiome is an integral part of human physiology; recent studies show that changes in the gut microbiota can modulate gastrointestinal physiology, immune function, and even behavior...
August 26, 2016: Biological Psychiatry
Xu-Zhao Li, Xu-Yan Yang, Yu Wang, Shuai-Nan Zhang, Wei Zou, Yan Wang, Xiao-Nan Li, Ling-Shu Wang, Zhi-Gang Zhang, Liang-Zhen Xie
OBJECTIVE: Oral lichen planus (OLP) is a relatively common chronic immune-pathological and inflammatory disease and potentially oral precancerous lesion. Erosive OLP patients show the higher rate of malignant transformation than patients with non-erosive OLP. Identifying the potential biomarkers related to erosive OLP may help to understand the pathogenesis of the diseases. METHODS: Metabolic profiles were compared in control and patient subjects with erosive OLP by using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods An integrative analysis was used to identify the perturbed metabolic pathways and pathological processes that may be associated with the disease...
October 17, 2016: Archives of Oral Biology
Arpa Surapaitoon, Sutas Suttiprapa, Narong Khuntikeo, Chawalit Pairojkul
The carcinogenic liver fluke Opisthorchis viverrini causes chronic inflammation in the bile duct and resulting in unremitting tissue damage that lead to hepatobiliary diseases, including cholangiocarcinoma (CCA). Despite inflammatory cytokine expression having been studied in the animal model, so far no studies have been carried out on cytokines in human CCA cases. Here we report the profile of cytokine production in peripheral blood mononuclear cells (PBMCs) collected from O. viverrini-associated human CCA and uninfected normal controls after stimulation with O...
October 18, 2016: Parasitology International
Carly B Garrison, Kristin J Lastwika, Yuzheng Zhang, Christopher I Li, Paul D Lampe
Proteomic studies can offer information on hundreds to thousands of proteins and potentially provide researchers with a comprehensive understanding of signaling response during stress and disease. Large datasets, such as those obtained in high-dimensional proteomic studies, can be leveraged for pathway analysis to discover or describe the biological implications of clinical disease states. Obesity is a worldwide epidemic that is considered a risk factor for numerous other diseases. We performed analysis on plasma proteomic data from 3 separate sample sets of post-menopausal women to identify the pathways that are altered in subjects with a high body mass index (BMI) compared to normal BMI...
October 21, 2016: Journal of Proteome Research
Shuaihantian Luo, Yunuo Wang, Ming Zhao, Qianjin Lu
Systemic lupus erythematosus (SLE) is a severe autoimmune disease that causes multiple-organ dysfunction mainly affecting women in their childbearing years. Type I IFN synthesis is usually triggered by viruses, and its production is tightly regulated and limited in time in health individuals. However, many patients with systemic autoimmune diseases including SLE have signs of aberrant production of type I interferon (IFN) and display an increased expression of IFN-inducible genes. Continuous type I IFNs derived from activated plasmacytoid dendritic cells (pDCs) by interferogenic immune complexes (ICs) and migration of these cells to tissues both break immune tolerance and promote an on-going autoimmune reaction in human body...
October 18, 2016: International Immunopharmacology
Valentina Talarico, Monica Aloe, Alice Monzani, Roberto Miniero, Gianni Bona
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy defined by thrombocytopenia, non-immune microangiopathic hemolytic anemia and acute renal failure. HUS is typically classified into two primary types: 1) HUS due to infections, often associated with diarrhea (D+HUS, Shiga toxin-producing Escherichia Coli-HUS), with the rare exception of HUS due to a severe disseminated infection caused by Streptococcus; 2) HUS related to complement, such HUS is also known as "atypical HUS" and is not diarrhea associated (D-HUS, aHUS); but recent studies have shown other forms of HUS, that can occur in the course of systemic diseases or physiopathological conditions such as pregnancy, after transplantation or after drug assumption...
December 2016: Minerva Pediatrica
Giuliana Giardino, Vera Gallo, Rosaria Prencipe, Giovanni Gaudino, Roberta Romano, Marco De Cataldis, Paola Lorello, Loredana Palamaro, Chiara Di Giacomo, Donatella Capalbo, Emilia Cirillo, Roberta D'Assante, Claudio Pignata
Increased risk of developing autoimmune manifestations has been identified in different primary immunodeficiencies (PIDs). In such conditions, autoimmunity and immune deficiency represent intertwined phenomena that reflect inadequate immune function. Autoimmunity in PIDs may be caused by different mechanisms, including defects of tolerance to self-antigens and persistent stimulation as a result of the inability to eradicate antigens. This general immune dysregulation leads to compensatory and exaggerated chronic inflammatory responses that lead to tissue damage and autoimmunity...
2016: Frontiers in Pediatrics
Giovanni Bernardini, Fabrizio Antonangeli, Valentina Bonanni, Angela Santoni
Chemokines are small chemotactic molecules that play key roles in physiological and pathological conditions. Upon signaling via their specific receptors, chemokines regulate tissue mobilization and trafficking of a wide array of immune cells, including natural killer (NK) cells. Current research is focused on analyzing changes in chemokine/chemokine receptor expression during various diseases to interfere with pathological trafficking of cells or to recruit selected cell types to specific tissues. NK cells are a heterogeneous lymphocyte population comprising several subsets endowed with distinct functional properties and mainly representing distinct stages of a linear development process...
2016: Frontiers in Immunology
Xiuqing Tian, Rui Guo, Yujiao Zhang, Lingling Xu, Xianbing Liu, Yinglong Hou
OBJECTIVE: To observe the effects of sympathetic overactivity on the immune system involved in the imbalance of T helper (Th) lymphocytes, we investigated the correlation between autonomic dysregulation and the generation of regulatory T (Treg) and Th1 chemokines in patients with acute coronary syndrome (ACS). METHODS: Blood samples obtained from patients with coronary artery disease and controls were analyzed for levels of Th1 and Treg cells and their associated cytokines by flow cytometry...
October 21, 2016: Neuroimmunomodulation
Yoshiyuki Goto, Satoshi Uematsu, Hiroshi Kiyono
Intestinal epithelial cells apically express glycans, especially α1,2-fucosyl linkages, which work as a biological interface for the host-microbe interaction. Emerging studies have shown that epithelial α1,2-fucosylation is regulated by microbes and by group 3 innate lymphoid cells (ILC3s). Dysregulation of the gene (FUT2) encoding fucosyltransferase 2, an enzyme governing epithelial α1,2-fucosylation, is associated with various human disorders, including infection and chronic inflammatory diseases. This suggests a critical role for an interaction between microbes, epithelial cells and ILC3s mediated via glycan residues...
October 19, 2016: Nature Immunology
Katherine A Dunn, Jessica Moore-Connors, Brad MacIntyre, Andrew Stadnyk, Nikhil A Thomas, Angela Noble, Gamal Mahdi, Mohsin Rashid, Anthony R Otley, Joseph P Bielawski, Johan Van Limbergen
BACKGROUND: Exclusive enteral nutrition (EEN) is a first-line therapy in pediatric Crohn's disease (CD) thought to induce remission through changes in the gut microbiome. With microbiome assessment largely focused on microbial taxonomy and diversity, it remains unclear to what extent EEN induces functional changes that thereby contribute to its therapeutic effect. METHODS: Fecal samples were collected from 15 pediatric CD patients prior to and after EEN treatment, as well as from 5 healthy controls...
November 2016: Inflammatory Bowel Diseases
Stuart G Tangye
Some autoimmune disorders are monogenetic diseases; however, clinical manifestations among individuals vary, despite the presence of identical mutations in the disease-causing gene. In this issue of the JCI, Massaad and colleagues characterized a seemingly monogenic autoimmune disorder in a family that was linked to homozygous loss-of-function mutations in the gene encoding the endonuclease Nei endonuclease VIII-like 3 (NEIL3), which has not been previously associated with autoimmunity. The identification of an unrelated healthy individual with the same homozygous mutation spurred more in-depth analysis of the data and revealed the presence of a second mutation in a known autoimmune-associated gene...
October 17, 2016: Journal of Clinical Investigation
Aran Singanayagam, Andrew I Ritchie, Sebastian L Johnston
PURPOSE OF REVIEW: The emergence of next-generation 16S rRNA sequencing techniques has facilitated a more detailed study of the body's microbiota and led to renewed interest in the association between microbial exposure and asthma inception. In this review, we evaluate the evidence that the respiratory tract and intestinal microbiota contribute to asthma pathogenesis and progression. RECENT FINDINGS: Human studies have revealed associations between the presence of potentially pathogenic bacteria in the respiratory tract in early life and subsequent risk of allergic sensitization and asthma...
October 15, 2016: Current Opinion in Pulmonary Medicine
Hagit Peleg, Eldad Ben-Chetrit
PURPOSE OF REVIEW: This article addresses the prevalence and relationship between autoinflammatory diseases and vasculitis. RECENT FINDINGS: Autoimmune diseases (AIDs) are a group of syndromes characterized by episodes of unprovoked inflammation due to dysregulation of the innate immune system. Despite the common occurrence of rashes and other skin lesions in these diseases, vasculitis is reported in only a few. On the other hand, neutrophilic dermatoses are more prevalent...
October 13, 2016: Current Opinion in Rheumatology
Jacinta L Johnson, Femke T A Buisman-Pijlman
The endogenous oxytocin system plays a vital role in facilitating parturition, lactation and social interaction in humans and other mammals. It also impacts on a number of important endocrine, immune and neurotransmitter systems. A well-regulated oxytocin system has been proposed to increase resilience, and therefore reduce the likelihood of an individual developing mental illness or substance dependence. This review discusses the adverse external influences that can modulate oxytocin receptor and protein levels and impact on substance use and mental health...
October 14, 2016: Behavioural Pharmacology
J M Parrott, L Redus, D Santana-Coelho, J Morales, X Gao, J C O'Connor
The kynurenine pathway of tryptophan metabolism has an important role in mediating the behavioral effects of inflammation, which has implications in understanding neuropsychiatric comorbidity and for the development of novel therapies. Inhibition of the rate-limiting enzyme, indoleamine 2,3-dioxygenase (IDO), prevents the development of many of these inflammation-induced preclinical behaviors. However, dysregulation in the balance of downstream metabolism, where neuroactive kynurenines are generated, is hypothesized to be a functionally important pathogenic feature of inflammation-induced depression...
October 18, 2016: Translational Psychiatry
Jong-Chan Youn
Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. Immunosenescence affects both the innate and adaptive immune systems; however, the most notable changes are in T cell immunity and include thymic involution, the collapse of T cell receptor (TCR) diversity, an imbalance in T cell populations, and the clonal expansion of senescent T cells. An increasing number of immunological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is associated with accelerated aging of the immune system and T cell immunosenescence especially...
September 2016: Journal of Hypertension
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