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Dan Xu, Andrew P Robinson, Toshiyuki Ishii, D'Anne S Duncan, Tord D Alden, Gwendolyn E Goings, Igal Ifergan, Joseph R Podojil, Pablo Penaloza-MacMaster, Jennifer A Kearney, Geoffrey T Swanson, Stephen D Miller, Sookyong Koh
The pathophysiology of drug-resistant pediatric epilepsy is unknown. Flow cytometric analysis of inflammatory leukocytes in resected brain tissues from 29 pediatric patients with genetic (focal cortical dysplasia) or acquired (encephalomalacia) epilepsy demonstrated significant brain infiltration of blood-borne inflammatory myeloid cells and memory CD4+ and CD8+ T cells. Significantly, proinflammatory (IL-17- and GM-CSF-producing) γδ T cells were concentrated in epileptogenic lesions, and their numbers positively correlated with disease severity...
February 27, 2018: Journal of Experimental Medicine
Ellen F Carney
No abstract text is available yet for this article.
February 26, 2018: Nature Reviews. Nephrology
Marisella Panduro, Christophe Benoist, Diane Mathis
Skeletal muscle regeneration is a highly orchestrated process that depends on multiple immune-system cell types, notably macrophages (MFs) and Foxp3+ CD4+ regulatory T (Treg ) cells. This study addressed how Treg cells rein in MFs during regeneration of murine muscle after acute injury with cardiotoxin. We first delineated and characterized two subsets of MFs according to their expression of major histocompatibility complex class II (MHCII) molecules, i.e., their ability to present antigens. Then, we assessed the impact of Treg cells on these MF subsets by punctually depleting Foxp3+ cells during the regenerative process...
February 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jing Geng, Shujuan Yu, Hao Zhao, Xiufeng Sun, Xun Li, Ping Wang, Xiaolin Xiong, Lixin Hong, Changchuan Xie, Jiahui Gao, Yiran Shi, Jiaqi Peng, Randy L Johnson, Nengming Xiao, Linrong Lu, Jiahuai Han, Dawang Zhou, Lanfen Chen
In the version of this article initially published, the institution name for affiliation 3 (Maryland Anderson Cancer Center) was incorrect. The correct institution is MD Anderson Cancer Center. The error has been corrected in the HTML and PDF versions of the article.
February 14, 2018: Nature Immunology
Keman Xu, William Y Yang, Gayani Kanchana Nanayakkara, Ying Shao, Fan Yang, Wenhui Hu, Eric T Choi, Hong Wang, Xiaofeng Yang
We conducted an experimental database analysis to determine the expression of 61 CD4+ Th subset regulators in human and murine tissues, cells, and in T-regulatory cells (Treg) in physiological and pathological conditions. We made the following significant findings: (1) adipose tissues of diabetic patients with insulin resistance upregulated various Th effector subset regulators; (2) in skin biopsy from patients with psoriasis, and in blood cells from patients with lupus, effector Th subset regulators were more upregulated than downregulated; (3) in rosiglitazone induced failing hearts in ApoE-deficient (KO) mice, various Th subset regulators were upregulated rather than downregulated; (4) aortic endothelial cells activated by proatherogenic stimuli secrete several Th subset-promoting cytokines; (5) in Treg from follicular Th (Tfh)-transcription factor (TF) Bcl6 KO mice, various Th subset regulators were upregulated; whereas in Treg from Th2-TF GATA3 KO mice and HDAC6 KO mice, various Th subset regulators were downregulated, suggesting that Bcl6 inhibits, GATA3 and HDAC6 promote, Treg plasticity; and (6) GATA3 KO, and Bcl6 KO Treg upregulated MHC II molecules and T cell co-stimulation receptors, suggesting that GATA3 and BCL6 inhibit Treg from becoming novel APC-Treg...
2018: Frontiers in Immunology
Harshit Khurana, Pankaj Malhotra, Man Updesh Sachdeva, Neelam Varma, Parveen Bose, Uday Yanamandra, Subhash Varma, Alka Khadwal, Deepesh Lad, Gaurav Prakash
OBJECTIVES: Danazol is an attenuated androgen and is used in the treatment of aplastic anemia (AA) in resource constraint settings. We chose to study the role of CD4+ CD25high CD127low FoxP3+ T regulatory cells (T-regs) in the pathophysiology of AA and their response to treatment with Danazol alone or in combination with immunosuppressive treatment (IST). METHODS: T-regs' percentages of 25 acquired idiopathic AA patients and 25 healthy controls who completed study protocol were analyzed by performing multicolor flowcytometry on peripheral blood samples...
February 8, 2018: Hematology (Amsterdam, Netherlands)
Sukhbir Manku, Wendy Wong, Zongshu Luo, Michael A Seidman, Zainab Alabdurubalnabi, Kevin Rey, Winnie Enns, J Antonio Avina-Zubieta, Kamran Shojania, Jonathan C Choy
Giant cell arteritis (GCA) is the most common vasculitis in adults affecting large and medium-sized arteries. IL-6 and T cell accumulation within the arterial wall contribute to the pathogenesis of GCA, and blockade of IL-6 activity is efficacious in its treatment. We examined the relationship between levels of IL-6 expression and immunological processes that control the expansion of T cells in GCA-positive temporal artery biopsies. CD4 T cells accumulated in clusters within the media and deep intima of all GCA lesions...
January 9, 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Souptik Barua, Penny Fang, Amrish Sharma, Junya Fujimoto, Ignacio Wistuba, Arvind U K Rao, Steven H Lin
OBJECTIVES: To determine the prognostic significance of spatial proximity of lung cancer cells and specific immune cells in the tumor microenvironment. MATERIALS AND METHODS: We probed formalin-fixed, paraffin-embedded (FFPE) tissue microarrays using a novel tyramide signal amplification multiplexing technique labelling CD8, CD4, Foxp3, and CD68+ cells. Each multiplex stained immunohistochemistry slide was digitally processed by Vectra INFORMS software, and an X- and Y-coordinate assigned to each labeled cell type...
February 3, 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Weiwei Fu, Xindong Liu, Xiang Lin, Han Feng, Lin Sun, Shuran Li, Hairong Chen, Hong Tang, Liwei Lu, Wei Jin, Chen Dong
T follicular regulatory (Tfr) cells are a new subset of regulatory T (T reg) cells localized in the germinal center to limit the humoral response. Until now, the physiological function of Tfr cells has been largely unknown. In this study, we developed a Bcl6fl/fl Foxp3Cre mouse to analyze the function of Tfr cells in immune and autoimmune responses. These mice exhibited enhanced immunity to influenza virus; moreover, Bcl6fl/fl Foxp3Cre/Cre mice developed late-onset spontaneous autoimmune diseases, affecting the salivary glands with lymphocyte infiltration and antibody deposition...
January 29, 2018: Journal of Experimental Medicine
Manish Bodas, Steven Mazur, Taehong Min, Neeraj Vij
BACKGROUND: Chronic lung disease resulting from dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) and NFκB-mediated neutrophilic-inflammation forms the basis of CF-related mortality. Here we aimed to evaluate if HDAC inhibition controls Pseudomonas-aeruginosa-lipopolysaccharide (Pa-LPS) induced airway inflammation and CF-lung disease. METHODS: For in vitro experiments, HEK293-cells were transfected with IL-8 or NFκB-firefly luciferase, and SV40-renilla- luciferase reporter constructs or ΔF508-CFTR-pCEP, followed by treatment with suberoylanilide hydroxamic acid (SAHA), Trichostatin-A (TSA) and/or TNFα...
January 4, 2018: Respiratory Research
Jennifer E Cowan, Song Baik, Nicholas I McCarthy, Sonia M Parnell, Andrea J White, William E Jenkinson, Graham Anderson
In the thymus, medullary thymic epithelial cells (mTEC) determine the fate of newly selected CD4+ and CD8+ single positive (SP) thymocytes. For example, mTEC expression of Aire controls intrathymic self-antigen availability for negative selection. Interestingly, alterations in both Foxp3+ Regulatory T-cells (T-Reg) and conventional SP thymocytes in Aire-/- mice suggest additional, yet poorly understood, roles for Aire during intrathymic T-cell development. To examine this, we analysed thymocytes from Aire-/- mice using Rag2GFP and Foxp3 expression, and a recently described CD69/MHCI subset definition of post-selection CD4+ conventional thymocytes...
December 29, 2017: European Journal of Immunology
Jason P Lynch, Rhiannon B Werder, Zhixuan Loh, Md Al Amin Sikder, Bodie Curren, Vivian Zhang, Matthew J Rogers, Katie Lane, Jennifer Simpson, Stuart B Mazzone, Kirsten Spann, John Hayball, Kerrilyn Diener, Mark L Everard, Christopher C Blyth, Christian Forstner, Paul G Dennis, Nida Murtaza, Mark Morrison, Páraic Ó Cuív, Ping Zhang, Ashraful Haque, Geoffrey R Hill, Peter D Sly, John W Upham, Simon Phipps
Respiratory syncytial virus-bronchiolitis is a major independent risk factor for subsequent asthma, but the causal mechanisms remain obscure. We identified that transient plasmacytoid dendritic cell (pDC) depletion during primary Pneumovirus infection alone predisposed to severe bronchiolitis in early life and subsequent asthma in later life after reinfection. pDC depletion ablated interferon production and increased viral load; however, the heightened immunopathology and susceptibility to subsequent asthma stemmed from a failure to expand functional neuropilin-1+ regulatory T (T reg) cells in the absence of pDC-derived semaphorin 4a (Sema4a)...
December 22, 2017: Journal of Experimental Medicine
Mariko Ishibashi, Hiromi Yamaguchi, Yukari Hirotani, Akihisa Sakurada, Toshihide Endo, Masahiko Sugitani, Tadatoshi Takayama, Makoto Makishima, Mariko Esumi
We found a HLA class II histocompatibility antigen gene, DQ alpha 1 chain (HLA-DQA1), that was expressed more than 9-fold higher in high-load hepatitis C virus (HCV) livers than low-load HCV livers using transcriptomics of chronic HCV-infected livers. To further investigate this finding, we examined which cells were positive for HLA-DQA1 and what liver immune responses were different between HCV-high and -low livers. HLA-DQA1-positive cells were significantly increased in the HCV-high group, and most positive cells were identified as non-parenchymal sinusoid cells and lymphocytic infiltrates in the portal area...
December 16, 2017: Archives of Virology
Bart N Lambrecht
In this issue Ohsaki et al. ( explain how breastfeeding can prevent the onset of food allergies in offspring by instructing T reg formation via neonatal Fc receptor (FcRn)-mediated transfer and uptake of allergen-containing IgG immune complexes (Ig-ICs) by gut dendritic cells (DCs).
January 2, 2018: Journal of Experimental Medicine
Amel Farwa, Chao He, Longfei Xia, Hong Zhou
In spite of long-term integrated control programs for Schistosoma japonicum infection in China, the infection is still persistent due to its zoonotic transmission and disease severity which further complicate its control. Th1, Th2, and T-reg cells are involved in S. japonicum immunity; however, their exact roles in immunopathology of this infection are still questionable. Therefore, the monitoring of these T cell subsets' immune responses during a primary infection of S. japonicum at both transcriptional (mRNA) and protein (cytokines) levels would be essential to point out...
January 2018: Parasitology Research
Asa Ohsaki, Nicholas Venturelli, Tess M Buccigrosso, Stavroula K Osganian, John Lee, Richard S Blumberg, Michiko K Oyoshi
The role of maternal immune responses in tolerance induction is poorly understood. To study whether maternal allergen sensitization affects offspring susceptibility to food allergy, we epicutaneously sensitized female mice with ovalbumin (OVA) followed by epicutaneous sensitization and oral challenge of their offspring with OVA. Maternal OVA sensitization prevented food anaphylaxis, OVA-specific IgE production, and intestinal mast cell expansion in offspring. This protection was mediated by neonatal crystallizable fragment receptor (FcRn)-dependent transfer of maternal IgG and OVA immune complexes (IgG-IC) via breast milk and induction of allergen-specific regulatory T (T reg) cells in offspring...
November 20, 2017: Journal of Experimental Medicine
Mona Fattouh, Asmaa N El-Din, Mohammed A El-Hamd
Psoriasis is one of the most common chronic, inflammatory, T-cell-mediated autoimmune diseases. Narrow-band UVB (NB-UVB) therapy is widely used in the treatment of psoriasis; however, its mechanism of action is still not well understood. The objective of this study was to investigate the circulating T-lymphocyte subpopulations in psoriasis patients before and after NB-UVB, to get insights into the mechanism of NB-UVB in the treatment of psoriasis. The severity of psoriasis was assessed by means of the Psoriasis Area and Severity Index (PASI-score)...
January 2017: Egyptian Journal of Immunology
Melissa Kasheta, Corrie A Painter, Finola E Moore, Riadh Lobbardi, Alysia Bryll, Eli Freiman, David Stachura, Arlin B Rogers, Yariv Houvras, David M Langenau, Craig J Ceol
Regulatory T (T reg) cells are a specialized sublineage of T lymphocytes that suppress autoreactive T cells. Functional studies of T reg cells in vitro have defined multiple suppression mechanisms, and studies of T reg-deficient humans and mice have made clear the important role that these cells play in preventing autoimmunity. However, many questions remain about how T reg cells act in vivo. Specifically, it is not clear which suppression mechanisms are most important, where T reg cells act, and how they get there...
December 4, 2017: Journal of Experimental Medicine
Jesse A Green, Nicholas Arpaia, Michail Schizas, Anton Dobrin, Alexander Y Rudensky
The involvement of effector T cells and regulatory T (T reg) cells in opposing and promoting solid organ carcinogenesis, respectively, is viewed as a shifting balance between a breach versus establishment of tolerance to tumor or self-antigens. We considered that tumor-associated T cells might promote malignancy via distinct mechanisms used by T cells in nonlymphoid organs to assist in their maintenance upon injury or stress. Recent studies suggest that T reg cells can participate in tissue repair in a manner separable from their immunosuppressive capacity...
December 4, 2017: Journal of Experimental Medicine
Alessandro Giardino, Giulio Innamorati, Stefano Ugel, Omar Perbellini, Roberto Girelli, Isabella Frigerio, Paolo Regi, Filippo Scopelliti, Giovanni Butturini, Salvatore Paiella, Matilde Bacchion, Claudio Bassi
OBJECTIVE/BACKGROUND: RFA of pancreatic cancer has been demonstrated to be feasible and safe with a positive impact on survival. The aim was to investigate whether an immune reaction is activated after locally advanced pancreatic cancer (LAPC) ablation. METHODS: Peripheral Blood samples were obtained preoperatively and on post-operative days 3-30. Evaluated parameters were: cells [CD4+, CD8+ and activated subsets, T-Reg, Monocytes, myeloid and plasmocytoid Dendritic cells (mDC and pDC)] and cytokines [Interleukin (IL)-6, Stromal-cells derived factor (SDF)-1, IL-1β, Tumour-Necrosis Factor (TNF)-α, Interferon (IFN)-γ, Vascular Endothelial Growth Factor (VEGF), chemokine (C-C motif) ligand 5 (CCL-5), Transforming-Growth Factor (TGF)-β]...
November 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
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