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https://www.readbyqxmd.com/read/29050947/cyclic-amp-responsive-element-binding-protein-creb-is-critical-in-autoimmunity-by-promoting-th17-but-inhibiting-treg-cell-differentiation
#1
Xiaohu Wang, Lu Ni, Dehui Chang, Huiping Lu, Yu Jiang, Byung-Seok Kim, Aibo Wang, Xindong Liu, Bo Zhong, Xuexian Yang, Chen Dong
The molecular mechanisms that govern differential T cell development into pro-inflammatory Th17 vs. regulatory T (Treg) cells remain unclear. Here, we show that selective deletion of CREB in T cells or Th17 cells impaired Th17 cell differentiation in vitro and in vivo, and led to resistance to autoimmune diseases. Mechanistically, CREB, activated by CD3-PKC-ϴ signaling, plays a key role in regulating Th17 cell differentiation, at least in part through directly binding to the Il17-Il17f gene locus. Unexpectedly, although dispensable for FOXP3 expression and for the homeostasis and suppressive function of thymus-derived Treg cells, CREB negatively regulates the survival of TGF-β-induced Treg cells, and deletion of CREB resulted in increased FOXP3+ Treg cells in the intestine and protection in a colitis model...
October 12, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29035123/physiopathology-and-genetics-in-aspirin-exacerbated-respiratory-disease
#2
Gandhi F Pavón-Romero, Fernando Ramírez-Jiménez, Marco Alejandro Roldán-Alvarez, Luis M Terán, Ramcés Falfán-Valencia
INTRODUCTION: Aspirin-exacerbated respiratory disease (AERD) is a clinical entity characterized by hypersensitivity to aspirin leading to asthma and chronic rhinosinusitis with nasosinusal polyposis. The pathophysiology of the disease involves disruption at the level of arachidonic acid metabolism. Therefore, genetic association studies have been focused on the genes coding this pathway. As other mechanisms involved in the genesis of the disease were elucidated, the corresponding genes were also explored...
October 16, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28979672/engrafted-peripheral-blood-derived-mesenchymal-stem-cells-promote-locomotive-recovery-in-adult-rats-after-spinal-cord-injury
#3
Qiang Fu, Yi Liu, Xiu Liu, Qian Zhang, Long Chen, Jiachen Peng, Jun Ao, Yuwan Li, Shengmin Wang, Gongyu Song, Limei Yu, Jinwei Liu, Tao Zhang
Spinal cord injury (SCI) is a severe trauma of central nervous system (CNS). Numerous stem cells have been applied for SCI therapy. Peripheral blood-derived mesenchymal stem cells (PBMSCs) have captured researchers' attention by virtue of pluripotency and effectiveness. However, little work has been performed on whether PBMSCs play roles and what role, if any, in the lesion microenvironment. Through the investigation of the differentiation, neuroprotection and immunoloregulation of engrafted PBMSCs, we found that the expression of glial fibrillary acidic protein (GFAP) was inhibited...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28955789/transcriptional-modulation-of-pattern-recognition-receptors-in-chronic-colitis-in-mice-is-accompanied-with-th1-and-th17-response
#4
Bin Zheng, Mary E Morgan, Hendrik J G van de Kant, Johan Garssen, Gert Folkerts, Aletta D Kraneveld
Pattern recognition receptors (PRRs) may contribute to inflammatory bowel diseases (IBD) development due to their microbial-sensing ability and the unique microenvironment in the inflamed gut. In this study, the PRR mRNA expression profile together with T cell-associated factors in the colon was examined using a chronic colitis mice model. 8-12 week old C57BL/6 mice were exposed to multiple dextran sodium sulfate (DSS) treatments interspersed with a rest period to mimic the course of chronic colitis. The clinical features and histological data were collected...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28944217/activation-of-inkt-cells-prevents-salmonella-enterocolitis-and-salmonella-induced-reactive-arthritis-by-downregulating-il-17-producing-%C3%AE-%C3%AE-t-cells
#5
Mariángeles Noto Llana, Sebastián H Sarnacki, Andrea L Morales, María Del R Aya Castañeda, Mónica N Giacomodonato, Guillermo Blanco, María C Cerquetti
Reactive arthritis (ReA) is an inflammatory condition of the joints that arises following an infection. Salmonella enterocolitis is one of the most common infections leading to ReA. Although the pathogenesis remains unclear, it is known that IL-17 plays a pivotal role in the development of ReA. IL-17-producers cells are mainly Th17, iNKT, and γδT lymphocytes. It is known that iNKT cells regulate the development of Th17 lineage. Whether iNKT cells also regulate γδT lymphocytes differentiation is unknown...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28937434/th17-response-of-borderline-lepromatous-leprosy-inhibits-rash-manifestation-of-dapsone-hypersensitivity-syndrome-case-report
#6
Tamara de Nardo Vanzela, Fred Bernardes Filho, Carlos Gustavo Wambier, Francesca Maia Faria, Norma Tiraboschi Foss, Marco Andrey Cipriani Frade
BACKGROUND: Dapsone hypersensitivity syndrome (DHS) is a rare, but potentially life-threatening reaction to dapsone. OBJECTIVE: Evaluation of immunological factors involved in the sparing of borderline-lepromatous (BL) leprosy patches by the severe exanthema related to DHS. METHODS: The authors describe a 19-year-old man with borderline-lepromatous leprosy with a recent diffuse rash, sparing only the hypochromic patches of leprosy, generalized lymphadenopathy, hepatomegaly, and jaundice 25 days after the start of multibacillary multidrug therapy...
September 11, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28935557/combination-of-pth-1-34-with-anti-il17-prevents-bone-loss-by-inhibiting-il-17-n-cadherin-mediated-disruption-of-pthr1-lrp-6-interaction
#7
Mohd Nizam Mansoori, Priyanka Shukla, Divya Singh
Combinations of anabolic and anti-resorptive agents have potential to improve bone density more than either agent alone. In this study, we determine the combining effect of anti-IL17 antibody and PTH (1-34) in mitigation of ovariectomy induced bone loss. Ovariectomized BALB/c female mice were treated with anti-IL17 and iPTH monotherapies and their combination. Combination of iPTH and anti-IL17 has synergistic effect in the restoration of skeletal and immune parameters compared to mono-therapies. Immunofluorescence analysis shows decreased expression of PTHR1 in iPTH+anti-IL17 treated bone sections...
September 19, 2017: Bone
https://www.readbyqxmd.com/read/28922472/mirna-506-promotes-primary-biliary-cholangitis-like-features-in-cholangiocytes-and-immune-activation
#8
Oihane Erice, Patricia Munoz-Garrido, Javier Vaquero, Maria J Perugorria, Maite G Fernandez-Barrena, Elena Saez, Alvaro Santos-Laso, Ander Arbelaiz, Raul Jimenez-Agüero, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Verónica Torrano, Arkaitz Carracedo, Meenakshisundaram Ananthanarayanan, Marco Marzioni, Jesus Prieto, Ulrich Beuers, Ronald P Oude Elferink, Nicholas F LaRusso, Luis Bujanda, Jose J G Marin, Jesus M Banales
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena targeting intrahepatic bile duct cells (cholangiocytes). Although PBC etiopathogenesis still remains obscure, development of anti-mitochondrial auto-antibodies against pyruvate dehydrogenase complex-E2 (PDC-E2) is a common feature. MicroRNA (miR) dysregulation occurs in liver and immune cells of PBC patients, but their functional relevance is largely unknown. We previously reported that miR-506 is overexpressed in PBC cholangiocytes and directly targets both Cl(-) /HCO3(-) anion exchanger 2 (AE2) and type III inositol 1,4,5-trisphosphate receptor (InsP3R3), leading to cholestasis...
September 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28919995/mammary-tumor-derived-ccl2-enhances-pro-metastatic-systemic-inflammation-through-upregulation-of-il1%C3%AE-in-tumor-associated-macrophages
#9
Kelly Kersten, Seth B Coffelt, Marlous Hoogstraat, Niels J M Verstegen, Kim Vrijland, Metamia Ciampricotti, Chris W Doornebal, Cheei-Sing Hau, Max D Wellenstein, Camilla Salvagno, Parul Doshi, Esther H Lips, Lodewyk F A Wessels, Karin E de Visser
Patients with primary solid malignancies frequently exhibit signs of systemic inflammation. Notably, elevated levels of neutrophils and their associated soluble mediators are regularly observed in cancer patients, and correlate with reduced survival and increased metastasis formation. Recently, we demonstrated a mechanistic link between mammary tumor-induced IL17-producing γδ T cells, systemic expansion of immunosuppressive neutrophils and metastasis formation in a genetically engineered mouse model for invasive breast cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28912720/a-single-angiotensin-ii-hypertensive-stimulus-is-associated-with-prolonged-neuronal-and-immune-system-activation-in-wistar-kyoto-rats
#10
Jasenka Zubcevic, Monica M Santisteban, Pablo D Perez, Rebeca Arocha, Helmut Hiller, Wendi L Malphurs, Luis M Colon-Perez, Ravindra K Sharma, Annette de Kloet, Eric G Krause, Marcelo Febo, Mohan K Raizada
Activation of autonomic neural pathways by chronic hypertensive stimuli plays a significant role in pathogenesis of hypertension. Here, we proposed that even a single acute hypertensive stimulus will activate neural and immune pathways that may be important in initiation of memory imprinting seen in chronic hypertension. We investigated the effects of acute angiotensin II (Ang II) administration on blood pressure, neural activation in cardioregulatory brain regions, and central and systemic immune responses, at 1 and 24 h post-injection...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28912510/the-th1-th17-balance-dictates-the-fibrosis-response-in-murine-radiation-induced-lung-disease
#11
Alexandra Paun, Marie-Eve Bergeron, Christina K Haston
Radiotherapy can result in lung diseases pneumonitis or fibrosis dependent on patient susceptibility. Herein we used inbred and genetically altered mice to investigate whether the tissue adaptive immune response to radiation injury influences the development of radiation-induced lung disease. Six inbred mouse strains were exposed to 18 Gy whole thorax irradiation and upon respiratory distress strains prone to pneumonitis with fibrosis presented an increased pulmonary frequency of Thelper (Th)17 cells which was not evident in strains prone solely to pneumonitis...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894116/characterization-of-tonsillar-il10-secreting-b-cells-and-their-role-in-the-pathophysiology-of-tonsillar-hypertrophy
#12
Lindybeth Sarmiento Varon, Javier De Rosa, Andrés Machicote, Luis Ariel Billordo, Plácida Baz, Pablo Mariano Fernández, Isabel Kaimen Maciel, Andrés Blanco, Eloísa I Arana
The comprehension of unconventional immune functions of tonsillar B cells, their role in tolerance induction and protective immune responses, is crucial to unveil the dynamic interactions of the upper aero digestive tract with polymicrobial commensal flora and pathogens, in health and disease. Here, we describe the kinetics of IL10 intracellular expression and compare it with that of cytokines known to be produced by tonsillar B cells. Additionally, we detected a relevant proportion of IL17-expressing tonsillar B cells, which has not previously been reported...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28882444/tetanus-toxoid-carrier-protein-induced-t-helper-cell-responses-upon-vaccination-of-middle-aged-adults
#13
Marieke van der Heiden, Aafke Duizendstra, Guy A M Berbers, Annemieke M H Boots, Anne-Marie Buisman
INTRODUCTION: Vaccines frequently induce suboptimal immune responses in the elderly, due to immunological ageing. Timely vaccination may be a strategy to overcome this problem, which classifies middle-aged adults asan interesting target group for future vaccine interventions. However, the immunological fitness of the middle-aged population is ill-defined. It is currently unknown whether effective T-cell help towards B-cells is initiated by conjugate-carrier vaccines at middle-age. AIM: We characterized systemic Tetanus Toxoid (TT) specific T-helper cell responses in the circulation of middle-aged adults (50-65years of age, n=31) having received the MenACWY-TT vaccination...
September 4, 2017: Vaccine
https://www.readbyqxmd.com/read/28876643/the-role-of-il17-a-in-the-second-hit-of-acute-pancreatitis
#14
J T Thomson, M B Brand, P FruFonteh
BACKGROUND: Acute pancreatitis is characterised by distinct clinical phases. An initial systemic inflammation response syndrome (SIRS) and occasional subsequent 'second hit' usually initiated by systemic sepsis. The pro-inflammatory T-helper 17 pathway has been shown to be an initiator of early SIRS in AP; however, to date, interleukin-17A has not been evaluated as a marker of the septic second hit in severe acute pancreatitis (SAP). METHOD: Twenty-five (aged 22-78) with mild (n = 12), moderate (n = 5) and severe (n = 8) acute pancreatitis were enrolled...
June 2017: South African Journal of Surgery. Suid-Afrikaanse Tydskrif Vir Chirurgie
https://www.readbyqxmd.com/read/28871249/neutralization-of-human-interleukin-23-by-multivalent-nanobodies-explained-by-the-structure-of-cytokine-nanobody-complex
#15
Aline Desmyter, Silvia Spinelli, Carlo Boutton, Michael Saunders, Christophe Blachetot, Hans de Haard, Geertrui Denecker, Maarten Van Roy, Christian Cambillau, Heidi Rommelaere
The heterodimeric cytokine interleukin (IL) 23 comprises the IL12-shared p40 subunit and an IL23-specific subunit, p19. Together with IL12 and IL27, IL23 sits at the apex of the regulatory mechanisms shaping adaptive immune responses. IL23, together with IL17, plays an important role in the development of chronic inflammation and autoimmune inflammatory diseases. In this context, we generated monovalent antihuman IL23 variable heavy chain domain of llama heavy chain antibody (VHH) domains (Nanobodies(®)) with low nanomolar affinity for human interleukin (hIL) 23...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28866816/distinctively-expressed-cytokines-by-three-different-inflammation-cells-and-their-interaction-with-keratinocytes-in-wound-healing
#16
Jingwen Wang, Xusheng Wang, Haiyan Chen, Jianjun Liu, Edward E Tredget, Yaojiong Wu
Inflammatory cells exert crucial influence on wound healing, while exploration is still desired to get further insight into the key factors that promote the process. In the present study, we performed comparative microarray data analysis of the three types of inflammatory cells isolated from skin wounds and focused on differentially expressed secreted factors. Gene Ontology enrichment and receptor analysis indicated that 11 genes of secreted factors in Ly6C(+) inflammatory macrophages and 27 genes of secreted factors in neutrophils exhibited higher (≥ 5-fold) expression, and all these factors were considered as candidates with potentially important role in keratinocyte activation...
September 2, 2017: Inflammation
https://www.readbyqxmd.com/read/28855306/il-23-drives-differentiation-of-peripheral-%C3%AE-%C3%AE-17-t-cells-from-adult-bone-marrow-derived-precursors
#17
Pedro H Papotto, Natacha Gonçalves-Sousa, Nina Schmolka, Andrea Iseppon, Sofia Mensurado, Brigitta Stockinger, Julie C Ribot, Bruno Silva-Santos
Pro-inflammatory interleukin (IL)-17-producing γδ (γδ17) T cells are thought to develop exclusively in the thymus during fetal/perinatal life, as adult bone marrow precursors fail to generate γδ17 T cells under homeostatic conditions. Here, we employ a model of experimental autoimmune encephalomyelitis (EAE) in which hematopoiesis is reset by bone marrow transplantation and demonstrate unequivocally that Vγ4(+) γδ17 T cells can develop de novo in draining lymph nodes in response to innate stimuli...
August 30, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28836262/immune-status-of-patients-with-haemophilia-a-before-exposure-to-factor-viii-first-results-from-the-hemfil-study
#18
MULTICENTER STUDY
Letícia L Jardim, Daniel G Chaves, Amanda C O Silveira-Cassette, Ana Cristina Simões E Silva, Marcio P Santana, Monica H Cerqueira, Alessandra Prezotti, Claudia Lorenzato, Vivian Franco, Johanna G van der Bom, Suely M Rezende
Previous cross-sectional studies showed that some patients with haemophilia A (HA) without inhibitor presented a pro-inflammatory profile during factor VIII (FVIII) replacement therapy. Furthermore, an anti-inflammatory/regulatory state was described in HA patients after inhibitor development. However, no study investigated the levels of these biomarkers before exposure to exogenous FVIII. This study investigated the immunological profile of previously untreated patients (PUPs) with HA in comparison with non-haemophiliac boys...
September 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28806280/integrated-analysis-of-biopsies-from-inflammatory-bowel-disease-patients-identifies-saa1-as-a-link-between-mucosal-microbes-with-th17-and-th22-cells
#19
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
https://www.readbyqxmd.com/read/28801611/pseudolaric-acid-b-attenuates-atopic-dermatitis-like-skin-lesions-by-inhibiting-interleukin-17-induced-inflammation
#20
Zhen Yang, Meilun Liu, Wei Wang, Yiteng Wang, Bo Cao, Ying Gao, Hong Chen, Tan Li
Pseudolaric acid B (PB), isolated from the extract of the root bark of Pseudolarix kaempferi Gordon, has been used as a traditional remedy for the treatment of skin diseases. However, the information of PB on atopic dermatitis (AD) remains largely unknown. In the present study, oral administration with PB improved the severity scores of AD-like skin lesions dose-dependently in NC/Nga mice through reducing serum IgE, pro-inflammatory cytokines, and the infiltration of inflammatory cells. In addition, PB significantly attenuated the levels of IL-17 and IL-22, and the proportion of Th17 cells in NC/Nga mice, as well as decreased IL-17-induced inflammation in RAW264...
August 11, 2017: Scientific Reports
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