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Garam Choi, Byung-Seok Kim, Young-Jun Park, Inbo Shim, Yeonseok Chung
The expansion of allergen-specific CD4(+) T cells is a critical step in inducing airway inflammation during allergic asthma. Such clonal expansion of T cells is initiated through the interaction between allergen-bearing dendritic cells and allergen-specific naïve T cells in the draining lymph nodes. Whether such T cell clonal expansion also occurs in the lung, the primary organ encountering inhaled allergens, remains unclear. Compared with wild-type mice, we found similar frequencies of CD4(+) T cells in the lung of lymph node-deficient Rorgt(gfp/gfp) mice after repeated exposure to inhaled allergens...
June 2017: Immune Network
Malin C Erlandsson, Sofia Töyrä Silfverswärd, Mitra Nadali, Minna Turkkila, Mattias N D Svensson, Ing-Marie Jonsson, Karin M E Andersson, Maria I Bokarewa
BACKGROUND: Signalling through insulin-like growth factor 1 receptor (IGF-1R) is essential for cell survival, but may turn pathogenic in uncontrolled tissue growth in tumours. In rheumatoid arthritis (RA), the IGF-1R signalling is activated and supports expansion of the inflamed synovia. AIM: In the present study, we assess if disruption of IGF-1R signalling resolves arthritis. MATERIAL AND METHODS: Clinical associations of IGF-1R expression in leukocytes of the peripheral blood were studied in 84 RA patients...
June 3, 2017: Biochimica et Biophysica Acta
Akiko Matsui-Hasumi, Yayoi Sato, Ayako Uto-Konomi, Satoshi Yamashita, Junji Uehori, Akihiko Yoshimura, Masakatsu Yamashita, Hiroshi Asahara, Shinobu Suzuki, Masato Kubo
IL-17 is known to be a cytokine mainly secreted from Th17 cells, which well associate with autoimmune inflammatory responses. In the generation of Th17 cells, RORc and RORa have pivotal roles in controlling the transcription of Il17. We speculated additional regulation in Il17a transcription and randomly screened a 6344 clone cDNA library to identify specific modulators for Il17a promoter activity. After the screen, the E3 ubiquitin ligases SIAH1 and SIAH2 were investigated further and confirmed to increase Il17a promoter activity in a T-cell line and to promote Th17 development ex vivo...
March 1, 2017: International Immunology
Kai Wang, Feng Jin, Zhanpu Zhang, Xiaochuan Sun
BACKGROUND Specific T cell phenotype has been reported to potentially contribute to the development of angiotensin II (Ang II)-induced several vascular disorders. Type 2 diabetes mellitus (T2DM) is intimately associated with cardiovascular disease. The present study aimed to investigate the relationship between T cell phenotypes and Ang II in T2DM patients combined with carotid atherosclerosis (CA). MATERIAL AND METHODS This study was performed on 50 patients with T2DM in our hospital. Based on the presence of CA, they were divided into CA group (presence of CA, n=30) or T2DM group (absence of CA, n=20)...
October 26, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
C F Wang, W T Yang, L M Yue, J Y Qiu, L J Zhang, C Wang, X Y Jiang, A D Qian
Nontuberculous mycobacteria are ubiquitous in outside environment and animals. As for nontuberculous mycobacteria infection, there is only limited information in humans regarding infection and the subsequent immune response, especially for Mycobacterium neoaurum. Here, haematoxylin-eosin and Ziehl-Neelsen staining were used to observe pathological changes and detect acid-fast bacilli in organ samples in mouse model. Flow cytometry and quantitative real-time polymerase chain reaction were performed to analyze the contribution of Th1, Th17 and Tregs to the host immune response...
September 23, 2016: Genetics and Molecular Research: GMR
Jiayin Yang, Lili Xu
BACKGROUND IL-23/IL-23R signaling plays a pivotal role during the course of inflammatory bowel diseases (IBD). However, the underlying mechanisms are poorly characterized. Foxp3+ regulatory T cells are critical in the maintenance of gut immune homeostasis and therefore are important in preventing the development of IBD. This study was performed to clarify the association between IL-23/IL-23R signaling and Foxp3+ regulatory T cells in colitis. MATERIAL AND METHODS Acute and chronic mouse colitis models were established by administering mice DSS in drinking water...
August 8, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Ekaterina Koroleva, Wayne Muraoka, Cody Spencer, Ekaterina Gubernatorova, Sydney Halperin, Scott Snapper, Alexei Tumanov
BACKGROUND: The balance between immune defense and inflammation in the gut is a highly regulated process that requires interactions between intestinal epithelial cells and the underlying immune system. RORgt+ group 3 innate lymphoid cells (ILC3s) have emerged as important regulators of intestinal inflammation. However, the signals that control the function of ILC3s are poorly understood. Recent studies revealed lymphotoxin (LT), a member of TNF family cytokines, as a novel regulator of ILC3s...
March 2016: Inflammatory Bowel Diseases
Charles Kivolowitz, Ahmed Abdulhamid, Daniel Victorio, Jim Castellanos, Kenneth Simpson, Ellen Scherl, Randy Longman
BACKGROUND: Spondyloarthritis (SpA) is the most common extra-intestinal manifestation in patients with inflammatory bowel disease (IBD), but the underlying pathogenesis that links IBD and SpA is unknown. Since IBD involves a dysregulated intestinal immune response to luminal microbial antigens and the abundance of particular microbial clades has been correlated to other arthropathies, we hypothesized that IBD-associated SpA (IBD-SpA) has a characteristic immunogenic microbial signature...
March 2016: Inflammatory Bowel Diseases
Chao Wang, Mary Collins, Vijay K Kuchroo
Effector CD4 T cell lineages have been implicated as potent inducers of autoimmune diseases. Tbet, Gata3 and Rorgt are master transcriptional regulators of Th1, Th2 and Th17 lineages respectively and promote the distinct expression of signature cytokines. Significant progress has been made in understanding the transcriptional network that drives CD4 T cell differentiation, revealing novel points of regulation mediated by transcription factors, cell surface receptors, cytokines and chemokines. Epigenetic modifications and metabolic mediators define the transcriptional landscape in which master transcription factors operate and collaborate with a network of transcriptional modifiers to guide lineage specification, plasticity and function...
December 2015: Current Opinion in Immunology
Jens Ingwersen, Til Menge, Britta Wingerath, Derya Kaya, Jonas Graf, Tim Prozorovski, Andreas Keller, Christina Backes, Markus Beier, Matthias Scheffler, Thomas Dehmel, Bernd C Kieseier, Hans-Peter Hartung, Patrick Küry, Orhan Aktas
OBJECTIVE: To identify microRNAs (miRNAs) regulated by anti-α4 integrin monoclonal antibody therapy (natalizumab) in the peripheral blood of patients with relapsing-remitting (RR) multiple sclerosis (MS) and to confirm their role in experimental settings in vivo. METHODS: In a longitudinal study of 17 RR-MS patients, we investigated blood miRNA expression profiles at baseline and after 1 year of natalizumab therapy by microarray technique and quantitative PCR validation...
January 2015: Annals of Clinical and Translational Neurology
A Zajícová, E Javorková, P Trošan, M Chudíčková, M Krulová, V Holáň
A low-molecular-weight (under 10 kDa) dialysable leukocyte extract (called transfer factor, TF) has been shown to be a prospective substance to improve or modulate immune response in autoimmunity, inflammation, infectious diseases or cancers. However, the use of TF has been limited by the absence of any data on the mechanism of its action. Here we show that TF prepared from peripheral blood leukocytes of healthy human donors displays multiple regulatory effects on individual parameters of the immune system...
2014: Folia Biologica (Praha)
Yoon Seok Roh, Surim Park, Chae Woong Lim, Bumseok Kim
BACKGROUND: Accumulating evidence suggests that Foxp3+ regulatory T (Treg) cells act as inhibitory mediators of inflammation; however, the in vivo mechanism underlying this protection remains elusive in liver diseases. AIMS: To clarify the in vivo role of Foxp3+ Treg cells in liver fibrosis, we used the DEREG mouse, which expresses the diphtheria toxin receptor under control of the Foxp3 promoter, allowing for specific deletion of Foxp3+ Treg cells. METHODS: Bile duct ligation-induced liver injury and fibrosis were assessed by histopathology, fibrogenic gene expression, and measurement of cytokine and chemokine levels...
July 2015: Digestive Diseases and Sciences
Serge A van de Pavert, Manuela Ferreira, Rita G Domingues, Hélder Ribeiro, Rosalie Molenaar, Lara Moreira-Santos, Francisca F Almeida, Sales Ibiza, Inês Barbosa, Gera Goverse, Carlos Labão-Almeida, Cristina Godinho-Silva, Tanja Konijn, Dennis Schooneman, Tom O'Toole, Mark R Mizee, Yasmin Habani, Esther Haak, Fabio R Santori, Dan R Littman, Stefan Schulte-Merker, Elaine Dzierzak, J Pedro Simas, Reina E Mebius, Henrique Veiga-Fernandes
The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood...
April 3, 2014: Nature
G C Furtado, M E Pacer, G Bongers, C Bénézech, Z He, L Chen, M C Berin, G Kollias, J H Caamaño, S A Lira
Lymphoid tissue often forms within sites of chronic inflammation. Here we report that expression of the proinflammatory cytokine tumor necrosis factor α (TNFα) drives development of lymphoid tissue in the intestine. Formation of this ectopic lymphoid tissue was not dependent on the presence of canonical RORgt(+) lymphoid tissue-inducer (LTi) cells, because animals expressing increased levels of TNFα but lacking RORgt(+) LTi cells (TNF/Rorc(gt)(-/-) mice) developed lymphoid tissue in inflamed areas. Unexpectedly, such animals developed several lymph nodes (LNs) that were structurally and functionally similar to those of wild-type animals...
May 2014: Mucosal Immunology
Matthias Lochner
In mammals, a variety of different lymphoid tissues have evolved as an integral part of the immune system that allows the host to survive in a sometimes hostile environment. While the development of secondary lymphoid organs is programmed in the fetus, the induction of other lymphoid structures like isolated lymphoid follicles (ILFs) in the gut or tertiary lymphoid tissues (tLT) need additional external triggers after birth. It is well established that for the development of secondary lymphoid organs, as well as ILFs, RORgt expressing lymphoid tissue inducer (LTi) cells play an important role...
May 2011: Gut Microbes
Tejas Patel, Vasu Patel, Rajvir Singh, Sundararajan Jayaraman
Epigenetic alteration of the genome has been shown to provide palliative effects in mouse models of certain human autoimmune diseases. We have investigated whether chromatin remodeling could provide protection against autoimmune diabetes in NOD mice. Treatment of female mice during the transition from prediabetic to diabetic stage (18-24 weeks of age) with the well-characterized histone deacetylase inhibitor, trichostatin A effectively reduced the incidence of diabetes. However, similar treatment of overtly diabetic mice during the same time period failed to reverse the disease...
July 2011: Immunology and Cell Biology
Takeshi Noma
The helper T cell paradigm, divided into two distinct subsets, Th1 and Th2 cells, characterized by distinct cytokine and functions, has been expanded to IL-17-producing Th17 cells. Th1 cells producing IFN-γ are involved in delayed-type hypersensitivity, effective in intracellular pathogens defense, while Th2 cells secrete IL-4, IL-5, IL-13 and IL-25 and has a central role in IgE production, eosinophilic inflammation, and the protection for helminthic parasite infection. Th17 cell lineages, expressing IL-17 family of cytokines and IL-23-mediated functions on T cells, plays a role in immune response to fungi and extracellular pathogens and autoimmune inflammatory disorders...
2010: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
Sundararajan Jayaraman, Tejas Patel, Vasu Patel, Shahnaz Ajani, Rebecca Garza, Arathi Jayaraman, Sung Kwon, Rajvir Singh, Damiano Rondelli, Bellur S Prabhakar, Mark Holterman
Although allogeneic bone marrow transplantation has been shown to prevent autoimmune diabetes in heavily irradiated nonobese diabetic (NOD) mice, a similar procedure is not suitable for the treatment of patients with type 1 diabetes because of associated severe side effects. Therefore, we evaluated whether mouse newborn blood (NBB), equivalent to human umbilical cord blood, could be used for diabetes prevention without recipient preconditioning. To test this hypothesis, unconditioned, prediabetic female NOD mice were given a single injection of whole NBB derived from the allogeneic diabetes-resistant mouse strain C57BL/6...
March 15, 2010: Journal of Immunology: Official Journal of the American Association of Immunologists
Bruno Silva-Santos, Daniel J Pennington, Adrian C Hayday
The thymus gives rise to two T cell lineages, alphabeta and gammadelta, that are thought to develop independently of one another. Hence, double positive (DP) thymocytes expressing CD4 and CD8 coreceptors are usually viewed simply as progenitors of CD4+ and CD8+ alphabeta T cells. Instead we report that DP cells regulate the differentiation of early thymocyte progenitors and gammadelta cells, by a mechanism dependent on the transcription factor RORgt, and the lymphotoxin (LT) beta receptor (LTbetaR). This finding provokes a revised view of the thymus, in which lymphoid tissue induction-type processes coordinate the developmental and functional integration of the two T cell lineages...
February 11, 2005: Science
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