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R Magliozzi, O W Howell, R Nicholas, C Cruciani, M Castellaro, C Romualdi, S Rossi, M Pitteri, M D Benedetti, A Gajofatto, F B Pizzini, S Montemezzi, S Rasia, R Capra, A Bertoldo, F Facchiano, S Monaco, R Reynolds, M Calabrese
OBJECTIVE: Grey matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in Multiple Sclerosis (MS), but can these changes be identified in the patient early in the disease course? METHODS: To identify possible biomarkers linking meningeal inflammation, GM damage and disease severity, gene and protein expression were analysed in meninges and CSF from 27 post-mortem secondary progressive MS (SPMS) and 14 control cases...
March 8, 2018: Annals of Neurology
Mari Kiyomatsu-Oda, Hiroshi Uchi, Saori Morino-Koga, Masutaka Furue
BACKGROUND: Chronic eczema such as atopic dermatitis imposes significant socio-econo-psychologic burdens on the affected individuals. In addition to conventional topical treatments, phototherapy is recommended for patients with extensive lesions. Although immunosuppression is believed to explain its primary effectiveness, the underlying mechanisms of phototherapy remain unsolved. Ultraviolet irradiation generates various tryptophan photoproducts including 6-formylindolo[3,2-b]-carbazole (FICZ)...
February 21, 2018: Journal of Dermatological Science
Svetlana Dambaeva, Sylvia Schneiderman, Mukesh K Jaiswal, Varkha Agrawal, Gajendra Katara, Alice Gilman-Sachs, Emmet Hirsch, Kenneth D Beaman
Preterm birth is widespread and causes 35% of all neonatal deaths. Infants who survive face potential long-term complications. A major contributing factor of preterm birth is infection. We investigated the role of Interleukin 22 (IL22) as a potential clinically relevant cytokine during gestational infection. IL22 is an effector molecule secreted by immune cells. While the expression of IL22 was reported in normal non-pregnant endometrium and early pregnancy decidua, little is known about uterine IL22 expression during mid- or late gestational stages of pregnancy...
January 5, 2018: Biology of Reproduction
W H Mai, X W Liu, G X Su, Z P Wen
Objective: To investigate the possible role of IL17-and IL22-secreting cells combined with patch test for the prediction of formaldehyde-induced occupational allergic contact dermatitis(OACD). Methods: From October 2014 to October 2016, totally 131 formaldehyde-exposed workers(49 cases with inflammatory skin lesions,82 ones without inflammatory skin lesions)and 63 non-exposed health controls were recruited. Patch-test was performed in 49 cases of formaldehyde-exposed workers with inflammatory skin lesions. Circulating IL17+and IL22+Tcell subsets were assessed by flow cytometry(FCM)...
October 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
Pau Morey, Lennart Pfannkuch, Ervinna Pang, Francesco Boccellato, Michael Sigal, Aki Imai-Matsushima, Victoria Dyer, Manuel Koch, Hans-Joachim Mollenkopf, Philipp Schlaermann, Thomas F Meyer
BACKGROUND & AIMS: Despite inducing an inflammatory response, Helicobacter pylori can persist in the gastric mucosa for decades. H pylori expression of cholesterol-α-glucosyltransferase (encoded by cgt) is required for gastric colonization and T-cell activation. We investigated how cgt affects gastric epithelial cells and the host immune response. METHODS: MKN45 gastric epithelial cells, AGS cells, and human primary gastric epithelial cells (obtained from patients undergoing gastrectomy or sleeve resection or gastric antral organoids) were incubated with interferon gamma (IFNG) or IFNB and exposed to H pylori, including cagPAI and cgt mutant strains...
December 19, 2017: Gastroenterology
Anna-Maj Albertsson, Xiaoli Zhang, Regina Vontell, Dan Bi, Roderick T Bronson, Veena Supramaniam, Ana A Baburamani, Sha Hua, Arshed Nazmi, Susanna Cardell, Changlian Zhu, Harvey Cantor, Carina Mallard, Henrik Hagberg, Jianmei W Leavenworth, Xiaoyang Wang
Brain injury in premature infants, especially periventricular leukomalacia, is an important cause of neurological disabilities. Inflammation contributes to the development of perinatal brain injury, but the essential mediators leading to brain injury in early life remain largely unknown. Neonates have reduced capacity for mounting conventional αβT-cell responses. However γδT-cells are already functionally competent during early development and are important in early life immunity. We investigated the potential contribution of γδT-cells to preterm brain injury by using postmortem brains from human preterm infants with periventricular leukomalacia and two animal models of preterm brain injury-the hypoxic-ischemic mouse model and a fetal sheep asphyxia model...
December 14, 2017: American Journal of Pathology
Dörte Kleinschmidt, Anastasios D Giannou, Heather M McGee, Jan Kempski, Babett Steglich, Francis Jessica Huber, Thomas Michael Ernst, Ahmad Mustafa Shiri, Claudia Wegscheid, Elena Tasika, Peter Hübener, Philipp Huber, Tanja Bedke, Niklas Steffens, Theodora Agalioti, Tobias Fuchs, Jill Noll, Hannelore Lotter, Gisa Tiegs, Ansgar W Lohse, Jonathan H Axelrod, Eithan Galun, Richard A Flavell, Nicola Gagliani, Samuel Huber
Acute liver injury can be secondary to a variety of causes, including infections, intoxication, and ischemia. All of these insults induce hepatocyte death and subsequent inflammation, which can make acute liver injury a life-threatening event. IL-22 is a dual natured cytokine which has context-dependent protective and pathogenic properties during tissue damage. Accordingly, IL-22 was shown to promote liver regeneration upon acute liver damage. However, other studies suggest pathogenic properties of IL-22 during chronic liver injury...
December 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Jose D Debes, Marjolein van Tilborg, Zwier M A Groothuismink, Bettina E Hansen, Julian Schulze Zur Wiesch, Johann von Felden, Robert J de Knegt, Andre Boonstra
Concern has arisen about the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs). To identify patients at risk for HCC, we evaluated serum levels of immune mediators before, during, and after DAA treatment of HCV infection. Our study included 13 patients who developed HCC within 18 months after treatment (3 with HCC recurrence and 10 with new HCC) and 10 patients who did not develop HCC (controls), within at least 24 months of treatment (median, 26 months)...
February 2018: Gastroenterology
Alessandra Geremia, Carolina V Arancibia-Cárcamo
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine that encompasses Crohn's disease (CD) and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC) in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses...
2017: Frontiers in Immunology
Marc Weidenbusch, Severin Rodler, Shangqing Song, Simone Romoli, Julian A Marschner, Franziska Kraft, Alexander Holderied, Santosh Kumar, Shrikant R Mulay, Mohsen Honarpisheh, Satish Kumar Devarapu, Maciej Lech, Hans-Joachim Anders
Notch and Interleukin-22 signaling are known to regulate tissue homeostasis and response to injury in humans and mice, and the induction of endogenous arylhydrocarbon receptor ligands through Notch links the two pathways in a hierarchical fashion. However, in adults the species-, organ- and injury-specific gene expression of the Notch-AhR-IL22 axis components is unknown. We therefore performed gene expression profiling of DLL1, DLL3, DLL4, DLK1, DLK2, JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, ADAM17/TACE, PSEN1, BSG/CD147, RBP-J, HES1, HES5, HEY1, HEYL, AHR, ARNT, ARNT2, CYP1A1, CYP24A1, IL22, IL22RA1, IL22RA2, IL10RB, and STAT3 under homeostatic conditions in 10 mature murine and human organs...
October 20, 2017: Bioscience Reports
Arezoo Gowhari Shabgah, Jamshid Gholizadeh Navashenaq, Omid Gohari Shabgah, Hamed Mohammadi, Amirhossein Sahebkar
Interleukin-22 (IL22) is one of the members of IL10 family. Elevated levels of this cytokine can be seen in diseases caused by T lymphocytes, such as Psoriasis, Rheumatoid arthritis, interstitial lung diseases. IL22 is produced by different cells in both innate and acquired immunities. Different types of T cells are able to produce IL22, but the major IL22-producing T-cell is the TCD4. TH22 cell is a new line of TCD4 cells, which differentiated from naive T cells in the presence of TNFα and IL6; 50% of peripheral blood IL22 is produced by these cells...
December 2017: Autoimmunity Reviews
Athumani M Ramadhani, Tamsyn Derrick, David Macleod, Patrick Massae, Tara Mtuy, David Jeffries, Chrissy H Roberts, Robin L Bailey, David C W Mabey, Martin J Holland, Matthew J Burton
Trachoma, caused by Chlamydia trachomatis, is the world's leading infectious cause of blindness and remains a significant public health problem. Much of trachomatous disease pathology is thought to be caused indirectly by host cellular and immune responses, however the immune response during active trachoma and how this initiates progressive scarring is not clearly understood. Defining protective vs. pathogenic immune response to C. trachomatis is important for vaccine design and evaluation. This study reports the baseline results of a longitudinal cohort of Tanzanian children, who were monitored for 4 years in order to determine the immunofibrogenic and infectious correlates of progressive scarring trachoma...
2017: Frontiers in Cellular and Infection Microbiology
Srabanti Rakshit, Vasista Adiga, Soumya Nayak, Pravat Nalini Sahoo, Prabhat Kumar Sharma, Krista E van Meijgaarden, Anto Jesuraj Uk J, Chirag Dhar, George D Souza, Greg Finak, Stephen C De Rosa, Tom H M Ottenhoff, Annapurna Vyakarnam
The functional heterogeneity of T cell responses to diverse antigens expressed at different stages of Mycobacterium tuberculosis (Mtb) infection, in particular early secreted versus dormancy related latency antigens expressed later, that distinguish subjects with latent (LTBI), pulmonary (PTB) or extrapulmonary (EPTB) tuberculosis remains unclear. Here we show blood central memory CD4 T-cell responses specific to Mtb dormancy related (DosR) latency, but not classical immunodominant secretory antigens, to clearly differentiate LTBI from EPTB and PTB...
September 20, 2017: Scientific Reports
Chunxu Gao, Bhanu Priya Ganesh, Zhongcheng Shi, Rajesh Rasik Shah, Robert Fultz, Angela Major, Susan Venable, Monica Lugo, Kathleen Hoch, Xiaowei Chen, Anthony Haag, Timothy C Wang, James Versalovic
Microbiome-mediated suppression of carcinogenesis may open new avenues for identification of therapeutic targets and prevention strategies in oncology. Histidine decarboxylase (HDC) deficiency has been shown to promote inflammation-associated colorectal cancer by accumulation of CD11b(+)Gr-1(+) immature myeloid cells, indicating a potential antitumorigenic effect of histamine. Here, we demonstrate that administration of hdc(+)Lactobacillus reuteri in the gut resulted in luminal hdc gene expression and histamine production in the intestines of Hdc(-/-) mice...
October 2017: American Journal of Pathology
Aaron R Victor, Ansel P Nalin, Wenjuan Dong, Susan McClory, Min Wei, Charlene Mao, Raleigh D Kladney, Youssef Youssef, Wing Keung Chan, Edward L Briercheck, Tiffany Hughes, Steven D Scoville, Jason R Pitarresi, Charlie Chen, Sarah Manz, Lai-Chu Wu, Jianying Zhang, Michael C Ostrowski, Aharon G Freud, Gustavo W Leone, Michael A Caligiuri, Jianhua Yu
Group 3 innate lymphoid cells (ILC3s) are important regulators of the immune system, maintaining homeostasis in the presence of commensal bacteria, but activating immune defenses in response to microbial pathogens. ILC3s are a robust source of IL-22, a cytokine critical for stimulating the antimicrobial response. We sought to identify cytokines that can promote proliferation and induce or maintain IL-22 production by ILC3s and determine a molecular mechanism for this process. We identified IL-18 as a cytokine that cooperates with an ILC3 survival factor, IL-15, to induce proliferation of human ILC3s, as well as induce and maintain IL-22 production...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Susanna Nikolaus, Berenice Schulte, Natalie Al-Massad, Florian Thieme, Dominik M Schulte, Johannes Bethge, Ateequr Rehman, Florian Tran, Konrad Aden, Robert Häsler, Natalie Moll, Gregor Schütze, Markus J Schwarz, Georg H Waetzig, Philip Rosenstiel, Michael Krawczak, Silke Szymczak, Stefan Schreiber
BACKGROUND & AIMS: Administration of tryptophan and some of its metabolites reduces the severity of colitis in mice, whereas removing tryptophan from the diet increases susceptibility to colitis. Transfer of the intestinal microbiome transfers the colitogenic phenotype from tryptophan starved animals to normally nourished mice. We aimed to systematically evaluate serum levels of tryptophan and its metabolites in patients with inflammatory bowel diseases (IBD), and study their association with clinical and serologic features...
December 2017: Gastroenterology
Mei San Tang, Rowann Bowcutt, Jacqueline M Leung, Martin J Wolff, Uma M Gundra, David Hudesman, Lisa B Malter, Michael A Poles, Lea Ann Chen, Zhiheng Pei, Antonio G Neto, Wasif M Abidi, Thomas Ullman, Lloyd Mayer, Richard A Bonneau, Ilseung Cho, Pʼng Loke
BACKGROUND: Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize and infer relationships between mucosal T cells, the host tissue environment, and microbial communities in patients with IBD who will serve as basis for mechanistic studies on human IBD. METHODS: We characterized mucosal CD4 T cells using flow cytometry, along with matching mucosal global gene expression and microbial communities data from 35 pinch biopsy samples from patients with IBD...
September 2017: Inflammatory Bowel Diseases
Morad Zayoud, Victoria Marcu-Malina, Einav Vax, Jasmine Jacob-Hirsch, Galit Elad-Sfadia, Iris Barshack, Yoel Kloog, Itamar Goldstein
The Ras family of GTPases plays an important role in signaling nodes downstream to T cell receptor and CD28 activation, potentially lowering the threshold for T-cell receptor activation by autoantigens. Somatic mutation in NRAS or KRAS may cause a rare autoimmune disorder coupled with abnormal expansion of lymphocytes. T cells from rheumatoid arthritis (RA) patients show excessive activation of Ras/MEK/ERK pathway. The small molecule farnesylthiosalicylic acid (FTS) interferes with the interaction between Ras GTPases and their prenyl-binding chaperones to inhibit proper plasma membrane localization...
2017: Frontiers in Immunology
Evgeny Chichelnitskiy, Britta Himmelseher, Malte Bachmann, Josef Pfeilschifter, Heiko Mühl
Disturbed homeostasis as a result of tissue stress can provoke leukocyte responses enabling recovery. Since mild hypothermia displays specific clinically relevant tissue-protective properties and interleukin (IL)-22 promotes healing at host/environment interfaces, effects of lowered ambient temperature on IL-22 were studied. We demonstrate that a 5-h exposure of endotoxemic mice to 4°C reduces body temperature by 5.0° and enhances splenic and colonic il22 gene expression. In contrast, tumor necrosis factor-α and IL-17A were not increased...
2017: Frontiers in Immunology
Weihua Mai, Xingwei Liu, Guangxiao Su, Wenying Zhou, Ziping Wen, Dongqing Lu
OBJECTIVES: The aim of this study was to investigate the effects of formaldehyde exposure on Th17 and Th22 cells and its relevance to human occupational allergic contact dermatitis (OACD). METHODS: Circulating IL17-/IL22-secreting cells and serum IL17/IL22 levels in formaldehyde-exposed workers at Occupational Exposure Limit and nonexposed controls were assessed. RESULTS: The IL17 and IL22 cell population were detected in both CD3CD8 and CD3CD8 cells...
July 10, 2017: Journal of Occupational and Environmental Medicine
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