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Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
Aditi Sharma, Pankaj Sharma, Laxmi Ganga, Neha Satoeya, Shikha Mishra, Achchhe Lal Vishwakarma, Mrigank Srivastava
Filarial parasites suppress, divert, or polarize the host immune response to aid their survival. However, mechanisms that govern the polarization of host MΦs during early filarial infection are not completely understood. In this study, we infected BALB/c mice with infective larvae stage-3 of Brugia malayi (Bm-L3) and studied their effect on the polarization of splenic MΦs. Results showed that MΦs displayed M2-phenotype by day 3 p.i. characterized by upregulated IL-4, but reduced IL-12 and Prostaglandin-D2 secretion...
2018: Frontiers in Immunology
Gargi Rai, Shukla Das, Mohammad Ahmad Ansari, Praveen Kumar Singh, Neelima Gupta, Sonal Sharma, Naseem Akhter, Vishnampettai G Ramachandran, Shafiul Haque, Sajad Ahmad Dar
Interleukin-17 producing T helper (Th17) and regulatory T cells (Treg) cells have been identified to play a critical role in atopic inflammation. However, conflicting reports on the role of Th17/Treg cells in allergic fungal rhinosinusitis (AFRS) patients of different ethnicities has mystified its pathogenesis. To better understand the pathophysiological mechanisms involved in AFRS, we conducted a prospective, analytical, case-control study involving 40 confirmed immunocompetent AFRS patients and 20 healthy controls...
February 20, 2018: International Immunopharmacology
Kathleen Yates, Kevin Bi, W Nicholas Haining, Harvey Cantor, Hye-Jung Kim
Regulatory T cells (Tregs) are key modulators of immune tolerance, capable of suppressing inflammatory immune responses and promoting nonlymphoid tissue homeostasis. Helios, a transcription factor (TF) that is selectively expressed by Tregs, has been shown to be essential for the maintenance of Treg lineage stability in the face of inflammatory conditions that include autoimmune disease and cancer. Helios-deficient Tregs within tumors acquire effector T cell function and contribute to immune responses against cancer...
February 27, 2018: Proceedings of the National Academy of Sciences of the United States of America
Hiroyuki Nagashima, Yuko Okuyama, Tsuyoshi Fujita, Takeo Takeda, Yasutaka Motomura, Kazuyo Moro, Takanori Hidaka, Koki Omori, Tsuyoshi Sakurai, Tomoaki Machiyama, Lishomwa C Ndhlovu, Carlo Riccardi, Takanori So, Naoto Ishii
No abstract text is available yet for this article.
February 7, 2018: Journal of Allergy and Clinical Immunology
Maran L Sprouse, Marissa A Scavuzzo, Samuel Blum, Ivan Shevchenko, Thomas Lee, George Makedonas, Malgorzata Borowiak, Matthew L Bettini, Maria Bettini
T cell receptor (TCR) affinity is a critical factor of Treg lineage commitment, but whether self-reactivity is a determining factor in peripheral Treg function remains unknown. Here, we report that a high degree of self-reactivity is crucial for tissue-specific Treg function in autoimmunity. Based on high expression of CD5, we identified a subset of self-reactive Tregs expressing elevated levels of T-bet, GITR, CTLA-4, and ICOS, which imparted significant protection from autoimmune diabetes. We observed that T-bet expression in Tregs, necessary for control of Th1 autoimmunity, could be induced in an IFNγ-independent fashion and, unlike in conventional T cells (Tconv), was strongly correlated with the strength of TCR signaling...
January 25, 2018: JCI Insight
Lucas C M Arruda, Kelen C R Malmegrim, João R Lima-Júnior, Emmanuel Clave, Juliana B E Dias, Daniela A Moraes, Corinne Douay, Isabelle Fournier, Hélène Moins-Teisserenc, Antônio José Alberdi, Dimas T Covas, Belinda P Simões, Pauline Lansiaux, Antoine Toubert, Maria Carolina Oliveira
To evaluate the immunological mechanisms associated with clinical outcomes after autologous hematopoietic stem cell transplantation (AHSCT), focusing on regulatory T- (Treg) and B- (Breg) cell immune reconstitution, 31 systemic sclerosis (SSc) patients underwent simultaneous clinical and immunological evaluations over 36-month posttransplantation follow-up. Patients were retrospectively grouped into responders (n = 25) and nonresponders (n = 6), according to clinical response after AHSCT. Thymic function and B-cell neogenesis were respectively assessed by quantification of DNA excision circles generated during T- and B-cell receptor rearrangements...
January 23, 2018: Blood Advances
Daniel O Villarreal, Michael J Allegrezza, Melissa A Smith, Diana Chin, Leopoldo L Luistro, Linda A Snyder
Mounting evidence demonstrates that CD8+CD122+ T cells have suppressive properties with the capacity to inhibit T cell responses. Therefore, these cells are rational targets for cancer immunotherapy. Here, we demonstrate that CD122 monoclonal antibody (mAb; aCD122) therapy significantly suppressed tumor growth and improved long-term survival in tumor-bearing mice. This therapeutic effect correlated with enhanced polyfunctional, cytolytic intratumoral CD8+ T cells and a decrease in granulocytic myeloid-derived suppressor cells (G-MDSCs)...
December 12, 2017: Oncotarget
Maran L Sprouse, Ivan Shevchenko, Marissa A Scavuzzo, Faith Joseph, Thomas Lee, Samuel Blum, Malgorzata Borowiak, Matthew L Bettini, Maria Bettini
Regulatory T cells (Tregs) use a distinct TCR repertoire and are more self-reactive compared with conventional T cells. However, the extent to which TCR affinity regulates the function of self-reactive Tregs is largely unknown. In this study, we used a two-TCR model to assess the role of TCR affinity in Treg function during autoimmunity. We observed that high- and low-affinity Tregs were recruited to the pancreas and contributed to protection from autoimmune diabetes. Interestingly, high-affinity cells preferentially upregulated the TCR-dependent Treg functional mediators IL-10, TIGIT, GITR, and CTLA4, whereas low-affinity cells displayed increased transcripts for Areg and Ebi3 , suggesting distinct functional profiles...
February 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Katia Beider, David Naor, Valeria Voevoda, Olga Ostrovsky, Hanna Bitner, Evgenia Rosenberg, Nira Varda-Bloom, Victoria Marcu-Malina, Jonathan Canaani, Ivetta Danilesko, Avichai Shimoni, Arnon Nagler
Polyclonal anti-human thymocyte globulins (ATG) have been recently shown to significantly reduce the incidence of graft versus host disease (GVHD) post allogeneic stem cell transplantation (HSCT) from both sibling and unrelated donors. Induction of regulatory T cells has been suggested as one of the possible mechanisms. The aim of current study was to further characterize the T cell populations induced by ATG treatment and to delineate the mechanisms involved in ATG-induced tolerance. Phenotypic characterization revealed a significant increase in the expression of FoxP3, GITR, CD95, PD-1 and ICOS as well as the complement inhibitory molecules CD55, CD58 and CD59 on CD4+CD25+ T cells upon ATG treatment...
October 31, 2017: Oncotarget
Chien-Hui Chien, Bor-Luen Chiang
Regulatory T cells play a crucial role in the homeostasis of the immune response. In addition to CD4+ Foxp3+ regulatory T cells, several subsets of Foxp3- regulatory T cells, such as T helper 3 (Th3) cells and type 1 regulatory T (Tr1) cells, have been described in mice and human. Accumulating evidence shows that naïve B cells contribute to tolerance and are able to promote regulatory T cell differentiation. Naïve B cells can convert CD4+ CD25- T cells into CD25+ Foxp3- regulatory T cells, named Treg-of-B cells by our group...
November 18, 2017: Journal of Biomedical Science
Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L Clouthier, Anh T Tran, Miguel S Torres Perez, Angela C Zhou, Ali A Abdul-Sater, Tania H Watts
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4+ T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs)...
November 21, 2017: Immunity
Samantha Burugu, Amanda R Dancsok, Torsten O Nielsen
The first generation of immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1) targeted natural immune homeostasis pathways, co-opted by cancers, to drive anti-tumor immune responses. These agents led to unprecedented results in patients with previously incurable metastatic disease and may become first-line therapies for some advanced cancers. However, these agents are efficacious in only a minority of patients. Newer strategies are becoming available that target additional immunomodulatory mechanisms to activate patients' own anti-tumor immune responses...
October 5, 2017: Seminars in Cancer Biology
Hui Li, Hai-Ying Chen, Wen-Xuan Liu, Xian-Xian Jia, Jing-Ge Zhang, Chun-Ling Ma, Xiao-Jing Zhang, Feng Yu, Bin Cong
Regulatory T cells (Treg cells) belong to a class of immunosuppressive cells that control the pathological changes of autoimmunity and inflammation. Prostaglandin E2 (PGE2) is a potent lipid mediator of immune inflammation including rheumatoid arthritis (RA) that exerts its effects via four subtypes of G-protein-coupled receptors (EP1-4). The ability of PGE2 to regulate human Treg differentiation has not yet been reported. In the current study, we investigated the effects of PGE2 on the differentiation of naïve T cells from healthy and RA patients into Treg cells and the intracellular signaling involved in this process in vitro...
September 28, 2017: Immunology Letters
W Wang, G Ji, Y Chen, J Wang, J Sun, G Tang, Z Xie, H Zhao, G Liu, S Tan, G Chen, H Xue
Liver transplantation (LT) is the criterion standard of care in patients with end-stage liver disease and those with tumors of hepatic origin in the setting of liver dysfunction. Chronic immune rejection of the liver transplant can lead to bad prognosis for patients. Glucocorticoid-induced tumor necrosis factor receptor (GITR) play a key role in dominant immunologic self-tolerance maintained by CD25+/CD4+ regulatory T cells. Here, we investigated the DNA methylation variations of GITR and GITR ligand (GITRL) using pyrosequencing by analyzing blood DNA samples of patients after LT...
October 2017: Transplantation Proceedings
Joana Cabral, Shirley A Hanley, Jared Q Gerlach, Neil O'Leary, Stephen Cunningham, Thomas Ritter, Rhodri Ceredig, Lokesh Joshi, Matthew D Griffin
Regulatory T-cells (Treg) are essential for maintaining immune homeostasis and tolerance. Surface glycosylation is ubiquitous on mammalian cells and regulates diverse biological processes. While it is currently well accepted that surface glycan expression influences multiple aspects of T-cell function, little is known about the relevance of glycosylation to Treg biology. This study aimed to profile the surface glycosylation characteristics of Treg in various lymphoid compartments of mouse and in human peripheral blood with comparison to non-regulatory, conventional CD4(+) T-cells (Tconv)...
2017: Frontiers in Immunology
Kai Yang, Daniel Bastardo Blanco, Geoffrey Neale, Peter Vogel, Julian Avila, Clary B Clish, Chuan Wu, Sharad Shrestha, Sherri Rankin, Lingyun Long, Anil Kc, Hongbo Chi
Regulatory T cells (Treg cells) have a pivotal role in the establishment and maintenance of immunological self-tolerance and homeostasis. Transcriptional programming of regulatory mechanisms facilitates the functional activation of Treg cells in the prevention of diverse types of inflammatory responses. It remains unclear how Treg cells orchestrate their homeostasis and interplay with environmental signals. Here we show that liver kinase B1 (LKB1) programs the metabolic and functional fitness of Treg cells in the control of immune tolerance and homeostasis...
August 31, 2017: Nature
Julius Clemens Fischer, Vera Otten, Maike Kober, Christoph Drees, Marc Rosenbaum, Martina Schmickl, Simon Heidegger, Rudi Beyaert, Geert van Loo, Xian Chang Li, Christian Peschel, Marc Schmidt-Supprian, Tobias Haas, Silvia Spoerl, Hendrik Poeck
Maintaining immune tolerance requires the production of Foxp3-expressing regulatory T (Treg) cells in the thymus. Activation of NF-κB transcription factors is critically required for Treg cell development, partly via initiating Foxp3 expression. NF-κB activation is controlled by a negative feedback regulation through the ubiquitin editing enzyme A20, which reduces proinflammatory signaling in myeloid cells and B cells. In naive CD4(+) T cells, A20 prevents kinase RIPK3-dependent necroptosis. Using mice deficient for A20 in T lineage cells, we show that thymic and peripheral Treg cell compartments are quantitatively enlarged because of a cell-intrinsic developmental advantage of A20-deficient thymic Treg differentiation...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Sadhna Aggarwal, Suresh C Sharma, Satya N Das
BACKGROUND AND OBJECTIVES: The immune dysfunction in oral squamous cell carcinoma (OSCC) patients is one of the major factors for growth and dissemination of tumor affecting disease-free survival. METHODS: The phenotypic and functional characteristics of Regulatory T (Treg ) CD4(+) CD25(+) FoxP3(+) subsets in OSCC patients were assessed by multicolor flow cytometry and its effector component (TGF-β) by Western blot and qRT-PCR. RESULTS: An increased (P < 0...
August 22, 2017: Journal of Surgical Oncology
Allison K Ehrlich, Jamie M Pennington, Susan Tilton, Xisheng Wang, Nikki B Marshall, Diana Rohlman, Castle Funatake, Sumit Punj, Edmond O'Donnell, Zhen Yu, Siva K Kolluri, Nancy I Kerkvliet
Activation of the aryl hydrocarbon receptor (AhR) by immunosuppressive ligands promotes the development of regulatory T (Treg) cells. Although AhR-induced Foxp3+ Treg cells have been well studied, much less is known about the development and fate of AhR-induced Type 1 Treg (AhR-Tr1) cells. In the current study, we identified the unique transcriptional and functional changes in murine CD4+ T cells that accompany the differentiation of AhR-Tr1 cells during the CD4+ T-cell-dependent phase of an allospecific cytotoxic T lymphocyte (allo-CTL) response...
November 2017: European Journal of Immunology
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