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Regulatory t cells

Nirjal Bhattarai, James H McLinden, Jinhua Xiang, M Meleah Mathahs, Warren N Schmidt, Thomas M Kaufman, Jack T Stapleton
Among human RNA viruses, hepatitis C virus (HCV) is unusual in that it causes persistent infection in the majority of infected people. To establish persistence, HCV evades host innate and adaptive immune responses by multiple mechanisms. Recent studies identified virus genome-derived small RNAs (vsRNAs) in HCV-infected cells; however, their biological significance during human HCV infection is unknown. One such vsRNA arising from the hepatitis C virus (HCV) E2 coding region impairs T cell receptor (TCR) signaling by reducing expression of a Src-kinase regulatory phosphatase (PTPRE) in vitro...
February 24, 2017: PLoS Pathogens
Varpu Elenius, Oscar Palomares, Matti Waris, Riitta Turunen, Tuomo Puhakka, Beate Rückert, Tytti Vuorinen, Tobias Allander, Tero Vahlberg, Mübeccel Akdis, Carlos A Camargo, Cezmi A Akdis, Tuomas Jartti
BACKGROUND: Tonsils have an active role in immune defence and inducing and maintaining tolerance to allergens. Vitamins A, D, and E, and antimicrobial peptide LL-37 may have immunomodulatory effects. We studied how their serum levels were associated with allergy status, intratonsillar/nasopharyngeal virus detection and intratonsillar expression of T cell- and innate immune response-specific cytokines, transcription factors and type I/II/III interferons in patients undergoing tonsillectomy...
2017: PloS One
Miho Mizuno, Daisuke Noto, Naoko Kaga, Asako Chiba, Sachiko Miyake
Autoimmune diseases are influenced by both genetic and environmental factors. The gut environment has attracted much attention as an essential component that modulates immune responses, and therefore immune-mediated disorders, such as autoimmune diseases. Growing evidence suggests that microbiota and their metabolites are critical factors for immune modulation. Recently, we reported that the microbiome in patients with multiple sclerosis, an autoimmune disease targeting the myelin sheath of the central nervous system, is characterized by a reduction of bacteria belonging to Clostridia clusters IV and XIVa, which are potent producers of short-chain fatty acids (SCFAs) by fermentation of indigestible carbohydrates...
2017: PloS One
Haruyo Nakajima-Adachi, Kyoko Shibahara, Yoko Fujimura, Jun Takeyama, Erika Hiraide, Akira Kikuchi, Hitoshi Murakami, Akira Hosono, Tomonori Nochi, Yoshio Wakatsuki, Naoki Shimojo, Shuichi Kaminogawa, Ryuichiro Sato, Hiroshi Kiyono, Satoshi Hachimura
BACKGROUND AND OBJECTIVE: The mechanism inducing either inflammation or tolerance to orally administered food allergens remains unclear. To investigate this we analyzed mouse models of food allergy (OVA23-3) and tolerance (DO11.10 [D10]), both of which express ovalbumin (OVA)-specific T-cell receptors. METHODS: OVA23-3, recombination activating gene (RAG)-2-deficient OVA23-3 (R23-3), D10, and RAG-2-deficient D10 (RD10) mice consumed a diet containing egg white (EW diet) for 2-28 days...
2017: PloS One
Marina A Afanasyeva, Lidia V Putlyaeva, Denis E Demin, Ivan V Kulakovskiy, Ilya E Vorontsov, Marina V Fridman, Vsevolod J Makeev, Dmitry V Kuprash, Anton M Schwartz
We studied functional effect of rs12722489 single nucleotide polymorphism located in the first intron of human IL2RA gene on transcriptional regulation. This polymorphism is associated with multiple autoimmune conditions (rheumatoid arthritis, multiple sclerosis, Crohn's disease, and ulcerative colitis). Analysis in silico suggested significant difference in the affinity of estrogen receptor (ER) binding site between alternative allelic variants, with stronger predicted affinity for the risk (G) allele. Electrophoretic mobility shift assay showed that purified human ERα bound only G variant of a 32-bp genomic sequence containing rs12722489...
2017: PloS One
Noureddine Idris-Khodja, Sofiane Ouerd, Michelle Trindade, Jordan Gornitsky, Asia Rehman, Tlili Barhoumi, Stefan Offermanns, Frank J Gonzalez, Mario F Neves, Pierre Paradis, Ernesto L Schiffrin
AIMS: Peroxisome proliferator-activated receptor γ (PPARγ) agonists reduce blood pressure and vascular injury in hypertensive rodents. Pparγ inactivation in vascular smooth muscle cells (VSMC) enhances vascular injury. Transgenic mice overexpressing endothelin (ET)-1 selectively in the endothelium (eET-1) exhibit endothelial dysfunction, increased oxidative stress and inflammation. We hypothesized that inactivation of the Pparγ gene in VSMC (smPparγ) would exaggerate ET-1-induced vascular injury...
February 22, 2017: Journal of Hypertension
Kari L Ring, Anna V Yemelyanova, Pamela T Soliman, Michael M Frumovitz, Amir A Jazaeri
OBJECTIVE: Our objective was to characterize the intra and peritumoral immune profile in recurrent cervical cancers to identify rational immunotherapy targets. METHODS: Archival pelvic exenteration specimens were examined using a validated multiplex immuno-fluorescent panel of antibodies against cluster of differentiation 8 (CD8), cluster of differentiation 68 (CD68), forkhead box P3 (FoxP3), programmed cell death protein 1 (PD1), and programmed death-ligand 1 (PD-L1, N=28)...
February 20, 2017: Gynecologic Oncology
Joe Yeong, Aye Aye Thike, Jeffrey Chun Tatt Lim, Bernett Lee, Huihua Li, Siew-Cheng Wong, Susan Swee Shan Hue, Puay Hoon Tan, Jabed Iqbal
PURPOSE: The role of Forkhead Box Protein 3 (Foxp3) expressing regulatory T cells (Tregs) in breast cancer remains unclear. We examined the abundance and localisation of total T cells, B cells and Tregs within samples from triple-negative breast cancers (TNBCs) and asked whether these parameters were associated with clinicopathological features of the cancer or clinical outcomes. METHODS: Samples from TNBCs diagnosed between 2003 and 2010 in Singapore were divided into "high" and "low" intra-tumoural or stromal groups, based on whether they had higher or lower than median densities of specific tumour-infiltrating lymphocyte populations (CD3(+) total T cells, Foxp3(+)CD3(+) Tregs, or CD20(+) B cells) in the intra-tumoural space or stroma...
February 23, 2017: Breast Cancer Research and Treatment
Bhalchandra Mirlekar, Dipendra Gautam, Samit Chattopadhyay
T cell differentiation from naïve T cells to specialized effector subsets of mature cells is determined by the iterative action of transcription factors. At each stage of specific T cell lineage differentiation, transcription factor interacts not only with nuclear proteins such as histone and histone modifiers but also with other factors that are bound to the chromatin and play a critical role in gene expression. In this review, we focus on one of such nuclear protein known as tumor suppressor and scaffold matrix attachment region-binding protein 1 (SMAR1) in CD4(+) T cell differentiation...
2017: Frontiers in Immunology
V L Ha, A Luong, F Li, D Casero, J Malvar, Y M Kim, R Bhatia, G M Crooks, C Parekh
The initial stages of T-cell differentiation are characterized by a progressive commitment to the T-cell lineage, a process that involves the loss of alternative (myelo-erythroid, NK, B) lineage potentials. Aberrant differentiation during these stages can result in T-cell acute lymphoblastic leukemia (T-ALL). However, the mechanisms regulating the initial stages of human T-cell differentiation are obscure. Through loss of function studies we showed BCL11B, a transcription factor recurrently mutated T-ALL, is essential for T-lineage commitment, particularly the repression of NK and myeloid potentials and the induction of T-lineage genes, during the initial stages of human T-cell differentiation...
February 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Soma Jyonouchi, Brenda Gwafila, Lavesh A Gwalani, Maria Ahmad, Chistopher Moertel, Cecil Holbert, Ji Young Kim, Nathan Kobrinsky, Sumita Roy-Ghanta, Jordan S Orange
BACKGROUND: Low dose IL-2 can restore the function of T and NK cells from Wiskott-Aldrich (WAS) patients.However, the safety of in vivo IL-2 in WAS is unknown. OBJECTIVES: A phase-I study to assess safety of low dose IL-2 in WAS. METHODS: Patients received 5 daily subcutaneous IL-2 injections, every 2months, for three courses.A "3+3" dose escalation method was used. RESULTS: 6 patients received the 0.5millionunits/m(2)/day dose without serious adverse events...
February 13, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Marianne von Euler Chelpin, Thomas Vorup-Jensen
Parkinson's Disease (PD) is the second most common neurodegenerative disease in the world, however, there is no cure for it. Current treatments only relieve some of the symptoms, without ceasing the disease, and lose efficacy with prolonged treatment. Considerable evidence shows that persistent inflammatory responses, involving T cell infiltration and glial cell activation, are common characteristics of human patients and play a crucial role in the degeneration of dopaminergic neurons. Therefore, it is important to develop therapeutic strategies that can impede or halt the disease through the modulation of the peripheral immune system by aiming at controlling the existing neuroinflammation...
February 23, 2017: Scandinavian Journal of Immunology
Bastian Höchst, Percy A Knolle
The immune system functions to defend the organism against infectious microorganisms but also against transformed cells. This key role of the immune system, in particular cancer-specific T cells, in eliminating cancer cells is compromised by various immune escape strategies employed by cancer cells and the cancer microenvironment. Here, we review the current knowledge about the immune escape mechanisms of cancer and the attempts to reconstitute cancer-specific immunity by using checkpoint inhibitors in head and neck squamous cell carcinoma...
February 24, 2017: ORL; Journal for Oto-rhino-laryngology and its related Specialties
Nicolas Ruffin, Lylia Hani, Nabila Seddiki
T follicular helper (Tfh) cells are essential for B cell differentiation and the subsequent antibody responses. Their numbers and functions are altered during human and simian immunodeficiency virus (HIV/SIV) infections. In lymphoid tissues, Tfh cells are present in germinal center, where they are the main source of replicative HIV-1 and represent a major reservoir. Paradoxically, Tfh numbers are increased in chronically infected individuals. Understanding the fate of Tfh cells in the course of HIV-1 infection is essential for the design of efficient strategies toward a protective HIV vaccine or a cure...
February 23, 2017: Immunology
Ana Cañete, Elena Cano, Ramón Muñoz-Chápuli, Rita Carmona
Vitamin A is an essential micronutrient throughout life. Its physiologically active metabolite retinoic acid (RA), acting through nuclear retinoic acid receptors (RARs), is a potent regulator of patterning during embryonic development, as well as being necessary for adult tissue homeostasis. Vitamin A deficiency during pregnancy increases risk of maternal night blindness and anemia and may be a cause of congenital malformations. Childhood Vitamin A deficiency can cause xerophthalmia, lower resistance to infection and increased risk of mortality...
February 20, 2017: Nutrients
Matthew T O'Brien, Jonathan S Oakhill, Naomi X Y Ling, Christopher G Langendorf, Ashfaqul Hoque, Toby A Dite, Anthony R Means, Bruce E Kemp, John W Scott
The Ca(2+)-calmodulin dependent protein kinase kinase-2 (CaMKK2) is a key regulator of neuronal function and whole-body energy metabolism. Elevated CaMKK2 activity is strongly associated with prostate and hepatic cancers, whereas reduced CaMKK2 activity has been linked to schizophrenia and bipolar disease in humans. Here we report the functional effects of nine rare-variant point mutations that were detected in large-scale human genetic studies and cancer tissues, all of which occur close to two regulatory phosphorylation sites and the catalytic site on human CaMKK2...
February 23, 2017: Scientific Reports
Joost F Swart, Eveline M Delemarre, Femke van Wijk, Jaap-Jan Boelens, Jürgen Kuball, Jacob M van Laar, Nico M Wulffraat
Autologous haematopoietic stem cell transplantation (HSCT) is the only treatment that is able to induce long-term, drug-free and symptom-free remission in several refractory autoimmune rheumatic diseases. Over 3,000 HSCT procedures for rheumatic and nonrheumatic severe autoimmune diseases have been performed worldwide. Specific conditioning regimens are currently used to eradicate the autoreactive immunological memory of patients. Although in vivo immune cell depletion with antithymocyte globulin or anti-CD52 is the norm for many regimens, ex vivo selection of CD34(+) stem cells from the graft is controversial...
February 23, 2017: Nature Reviews. Rheumatology
Maciej M Markiewski, Surya Kumari Vadrevu, Sharad K Sharma, Navin Kumar Chintala, Shanawaz Ghouse, Jun-Hung Cho, David P Fairlie, Yvonne Paterson, Aristotelis Astrinidis, Magdalena Karbowniczek
Relatively little is known about factors that initiate immunosuppression in tumors and act at the interface between tumor cells and host cells. In this article, we report novel immunosuppressive properties of the ribosomal protein S19 (RPS19), which is upregulated in human breast and ovarian cancer cells and released from apoptotic tumor cells, whereupon it interacts with the complement C5a receptor 1 expressed on tumor infiltrating myeloid-derived suppressor cells. This interaction promotes tumor growth by facilitating recruitment of these cells to tumors...
February 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Zhongmei Zhang, Wei Zhang, Jie Guo, Qianchong Gu, Xueping Zhu, Xuyu Zhou
Accumulating evidence suggests that Foxp3(+) cells can downregulate the expression of Foxp3, but whether thymically derived regulatory T cells (tTregs; especially committed tTregs) are capable of downregulating Foxp3 expression and being reprogrammed into other T effector cells remains controversial. Using a novel tTreg lineage-tracing mouse line, we were able to label epigenetically stable Foxp3(+) cells derived from the thymus and demonstrate that mature tTregs are stable under homeostatic conditions. However, TCR engagement and sequential functional specialization of tTregs led to the generation of Foxp3 instability and reprogramming into the Th lineage...
February 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Jennifer C Dennis-Wall, Tyler Culpepper, Carmelo Nieves, Cassie C Rowe, Alyssa M Burns, Carley T Rusch, Ashton Federico, Maria Ukhanova, Sheldon Waugh, Volker Mai, Mary C Christman, Bobbi Langkamp-Henken
Background: Rhinoconjunctivitis-specific quality of life is often reduced during seasonal allergies. The Mini Rhinoconjunctivitis Quality of Life Questionnaire (MRQLQ) is a validated tool used to measure quality of life in people experiencing allergies (0 = not troubled to 6 = extremely troubled). Probiotics may improve quality of life during allergy season by increasing the percentage of regulatory T cells (Tregs) and inducing tolerance.Objective: The objective of this study was to determine whether consuming Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and B...
February 22, 2017: American Journal of Clinical Nutrition
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