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K Kajikhina, M Tsuneto, F Melchers
Early in embryonic development of mice, from day 12.5 after conception, myeloid-lymphoid bipotent progenitors, expressing receptors both for IL7 and CSF-1, migrate from embryonic blood into developing fetal liver. These progenitors also express multiple chemokine receptors, i.e., CCR7, CXCR3, CXCR4, and CXCR5, all on one cell. Their migration through LYVE-1+ vascular endothelium is guided by CCR7, recognizing the chemokine CCL19, and by CXCR3, recognizing CXCL10/11, chemokines which are both produced by the endothelium...
2016: Advances in Immunology
Deying Liu, Jinxiang Liu, Jinghua Wang, Congcong Liu, Sirui Yang, Yanfang Jiang
BACKGROUND: Circulating follicular helper T (Tfh) cells are a heterogeneous population of CD4(+) helper T cells that promotes pathogenic immune responses in autoimmune diseases. In this study, we examined the status of different subpopulations of Tfh cells in peripheral circulation and their associations with various clinical characteristics of IgA vasculitis (IgAV). METHODS: According to the phenotypic expressions of different molecules, focus was given on six subpopulations of Tfh cells: CD4(+)CXCR5(+), CD4(+)CXCR5(+)ICOS(+), CD4(+)CXCR5(+)ICOS(+)PD-1(+), CD4(+)CXCR5(+)ICOS(high)PD-1(high), CD4(+)CXCR5(+)ICOS(-)PD-1(+), and CXCR5(+)CD45RA(-)IL-21(+)...
October 21, 2016: BMC Immunology
Ran He, Shiyue Hou, Cheng Liu, Anli Zhang, Qiang Bai, Miao Han, Yu Yang, Gang Wei, Ting Shen, Xinxin Yang, Lifan Xu, Xiangyu Chen, Yaxing Hao, Pengcheng Wang, Chuhong Zhu, Juanjuan Ou, Houjie Liang, Ting Ni, Xiaoyan Zhang, Xinyuan Zhou, Kai Deng, Yaokai Chen, Yadong Luo, Jianqing Xu, Hai Qi, Yuzhang Wu, Lilin Ye
No abstract text is available yet for this article.
October 19, 2016: Nature
Norikazu Kiguchi, Huiping Ding, Christopher M Peters, Nancy D Kock, Shiroh Kishioka, J Mark Cline, Janice D Wagner, Mei-Chuan Ko
Neuroinflammation is a pathological condition that underlies diabetes and affects sensory processing. Given the high prevalence of pain in diabetic patients and crosstalk between chemokines and opioids, it is pivotal to know whether neuroinflammation-associated mediators are dysregulated in the central nervous system of diabetic primates. Therefore, the aim of this study was to investigate whether mRNA expression levels of glial markers, chemokines, and opioid receptors are altered in the spinal cord and thalamus of naturally occurring type 2 diabetic monkeys (n=7) compared with age-matched non-diabetic monkeys (n=6)...
October 14, 2016: Biochimica et Biophysica Acta
Young Uk Kim, Byung-Seok Kim, Hoyong Lim, Rick A Wetsel, Yeonseok Chung
CXCR5⁺ T follicular helper (Tfh) cells are associated with aberrant autoantibody production in patients with antibody-mediated autoimmune diseases including lupus. Follicular regulatory T (Tfr) cells expressing CXCR5 and Bcl6 have been recently identified as a specialized subset of Foxp3⁺ regulatory T (Treg) cells that control germinal center reactions. In this study, we show that retroviral transduction of CXCR5 gene in Foxp3⁺ Treg cells induced a stable expression of functional CXCR5 on their surface...
October 17, 2016: Biomolecules & Therapeutics
Xiao-Bo Wu, De-Li Cao, Xin Zhang, Bao-Chun Jiang, Lin-Xia Zhao, Bin Qian, Yong-Jing Gao
CXCL13 is a B lymphocyte chemoattractant and activates CXCR5 receptor in the immune system. Here we investigated whether CXCL13/CXCR5 mediates inflammatory pain in dorsal root ganglia (DRG) and the underlying mechanisms. Peripheral injection of complete Freund's Adjuvant (CFA) increased the expression of CXCL13 and CXCR5 in DRG neurons. In Cxcr5(-/-) mice, CFA-induced pain hypersensitivity were attenuated. Whole-cell patch-clamp recording showed that the excitability of dissociated DRG neurons was increased after CFA injection or CXCL13 incubation from wild-type (WT) mice, but not from Cxcr5(-/-) mice...
October 6, 2016: Scientific Reports
Michel Varrin-Doyer, Kara L Pekarek, Collin M Spencer, Claude C A Bernard, Raymond A Sobel, Bruce A C Cree, Ulf Schulze-Topphoff, Scott S Zamvil
OBJECTIVE: To evaluate the influence of oral laquinimod, a candidate multiple sclerosis (MS) treatment, on induction of T follicular helper cells, development of meningeal B cell aggregates, and clinical disease in a spontaneous B cell-dependent MS model. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by immunization with recombinant myelin oligodendrocyte glycoprotein (rMOG) protein. Spontaneous EAE was evaluated in C57BL/6 MOG p35-55-specific T cell receptor transgenic (2D2) × MOG-specific immunoglobulin (Ig)H-chain knock-in (IgH(MOG-ki) [Th]) mice...
October 2016: Neurology® Neuroimmunology & Neuroinflammation
Liting Tian, Qilin Fu, Fu Huang
The aim of the present study was to investigate the T cell immune function in chronic hepatitis B hepatocirrhosis patients at the compensated and decompensated stage following treatment with adefovir dipivoxil. A total of 104 patients diagnosed with hepatitis B hepatocirrhosis during the period from October 2013 to October 2014 were enrolled in the study. Among the cases, there were 56 cases at compensated stage, and another 48 at decompensated stage. Adefovir dipivoxil was administered for antiviral therapy (10 mg/time, 1 time/day, for a total of 24 weeks), and we compared the virus disappearance rate, liver function improvement and T cell immune function between the two groups before and after treatment...
October 2016: Experimental and Therapeutic Medicine
Saleh A Bakheet, Mohammad Zeed Alzahrani, Ahmed Nadeem, Mushtaq Ahmad Ansari, Khairy M A Zoheir, Sabry M Attia, Laila Yousef Al-Ayadhi, Sheikh Fayaz Ahmad
Autism is a neurodevelopmental disorder categorized by qualitative impairments in social interaction, communication, and repetitive stereotypic behavior. Emerging evidence increasingly suggests that chemokine receptors have a pivotal role in the central nervous system and are involved in the pathogenesis of numerous neuroinflammatory diseases. Resveratrol is widely used to treat neurodegenerative diseases, but its effect on autism has not been investigated. We investigated the effect of resveratrol (20 and 40mg/kg) in the spleen and brain tissues of BTBR T+tf/J (BTBR) and C57BL/6J (B6) mice as well as on the C-C chemokine receptor (CCR) and C-X-C motif chemokine receptor (CXCR) (CCR3(+), CCR5(+), CCR7(+) and CCR9(+), CXCR3(+) and CXCR5(+)) in cluster of differentiation 4-positive (CD4(+)) T cells in the spleen...
September 29, 2016: Molecular and Cellular Neurosciences
Zhanyun Da, Liuxia Li, Jin Zhu, Zhifeng Gu, Bo You, Ying Shan, Si Shi
As a CXC subtype member of the chemokine superfamily, CXCL13 is considered to be involved in systemic lupus erythematosus (SLE), especially in lupus nephritis (LN). To determine the effect of CXCL13 on SLE and explore the potential mechanisms, we tested serum concentrations of CXCL13 in patients and healthy individuals and found that CXCL13 expression was high in SLE patients especially in LN patients. When we treated human renal mesangial cells (HRMCs) in vitro with recombinant human CXCL13, the cell proliferation was accelerated, which was tested by Cell Counting Kit-8 assay and flow cytometry...
2016: Journal of Immunology Research
Ilona Kryczek, Lin Wang, Ke Wu, Wei Li, Ende Zhao, Tracy Cui, Shuang Wei, Yan Liu, Yin Wang, Linda Vatan, Wojciech Szeliga, Joel K Greenson, Jacek Roliński, Witold Zgodzinski, Emina Huang, Kaixiong Tao, Guobin Wang, Weiping Zou
Foxp3(+)CD4(+) regulatory T (Treg) cells are thought to express negligible levels of effector cytokines, and inhibit immune responses and inflammation. Here, we have identified a population of IL-8(+)Foxp3(+)CD4(+) T cells in human peripheral blood, which is selectively increased in the microenvironments of ulcerative colitis and colon carcinoma. Phenotypically, this population is minimally overlapping with IL-17(+)Foxp3(+)CD4(+) T cells, and is different from IL-8(-)Foxp3(+)CD4(+) T cells in the same microenvironment...
August 2016: Oncoimmunology
Yu Lei, Tingting Hu, Xiaofei Song, Hong Nie, Min Chen, Weixian Chen, Zhi Zhou, Dazhi Zhang, Huaidong Hu, Peng Hu, Hong Ren
T follicular helper cells (Tfh) provide help to B cells to support their activation, expansion and differentiation. However, the role of Tfh cells in chronic HBV infection is poorly defined. The aim of this research was to examine the function of Tfh cells and whether they are involved in HBV related disease. Blood CXCR5+CD4+T cells and B cells in 85 patients with chronic HBV infection (HBV patients) and health controls (HC) were examined by flow cytometry. The molecule expression in blood CXCR5+CD4+ T cells was detected by real-time PCR...
2016: PloS One
Alicia Beatriz Costantino, Cristina Del Valle Acosta, Laura Onetti, Eduardo Mussano, Ignacio Isaac Cadile, Paola Virginia Ferrero
INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by the presence of different autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies. CD4T cells expressing CXCR5, referred as follicular helper T cells (Tfh), collaborate with B cells to produce antibodies. Differential expression of CXCR3 and CCR6 within CD4(+)CXCR5(+) T cells defines three mayor subsets: CXCR3(+)CCR6(-) (Tfh1), CXCR3(-)CCR6(-) (Tfh2) and CXCR3(-)CCR6(+) (Tfh17)...
August 29, 2016: Reumatología Clinica
Elisa Ferretti, Maurilio Ponzoni, Claudio Doglioni, Vito Pistoia
The germinal center (GC) is a dynamic structure formed by proliferating B cells in the follicles of secondary lymphoid organs during T cell-dependent antibody responses to exogenous antigens. GC is composed by a dark zone, enriched in proliferating centroblasts (CBs), and a light zone where CBs migrate and transform into centrocytes (CCs), a minority of which is selected to survive, undergoes Ig class-switch recombination, and differentiates into memory B cells or long-lived plasma cells. CBs express CXCR4 and are attracted to the dark zone by stromal cell-derived CXCL12, whereas CCs express CXCR5 and are recruited to the light zone along a gradient of CXCL13 produced by follicular dendritic cells (FDCs)...
August 26, 2016: Journal of Leukocyte Biology
Vanessa Sue Wacleche, Jean-Philippe Goulet, Annie Gosselin, Patricia Monteiro, Hugo Soudeyns, Rémi Fromentin, Mohammad-Ali Jenabian, Shant Vartanian, Steven G Deeks, Nicolas Chomont, Jean-Pierre Routy, Petronela Ancuta
BACKGROUND: Th17 cells are permissive to HIV-1 infection and their depletion from the gut of infected individuals leads to microbial translocation, a major cause for non-AIDS co-morbidities. Most recent evidence supports the contribution of long-lived Th17 cells to HIV persistence during antiretroviral therapy (ART). However, the identity of long-lived Th17 cells remains unknown. RESULTS: Here, we performed an in-depth transcriptional and functional characterization of four distinct Th17 subsets and investigated their contribution to HIV reservoir persistence during ART...
2016: Retrovirology
Cun-Jin Zhang, Ye Gong, Wenli Zhu, Yuan Qi, Chun-Sheng Yang, Ying Fu, Guoqiang Chang, Yujing Li, Samuel Shi, Kristofer Wood, Shafeeq Ladha, Fu-Dong Shi, Qiang Liu, Yaping Yan
Myasthenia gravis (MG) is a chronic humoral immunity-mediated autoimmune disorder of the neuromuscular junction characterized by muscle weakness. Follicular helper T (Tfh) cells may be the key Th cell subset that promotes MG development, as their major function is helping B cell activation and Ab production. Aberrance of thymus-derived Tfh cells might be implicated in autoimmune diseases including MG; just how circulating Tfh cells, especially those from patients with a normal thymus, contribute to MG pathogenesis remains to be uncovered...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Shuang Wu, Sophia R Majeed, Timothy M Evans, Marine D Camus, Nicole M L Wong, Yvette Schollmeier, Minjong Park, Jagan R Muppidi, Andrea Reboldi, Peter Parham, Jason G Cyster, Frances M Brodsky
Clathrin, a cytosolic protein composed of heavy and light chain subunits, assembles into a vesicle coat, controlling receptor-mediated endocytosis. To establish clathrin light chain (CLC) function in vivo, we engineered mice lacking CLCa, the major CLC isoform in B lymphocytes, generating animals with CLC-deficient B cells. In CLCa-null mice, the germinal centers have fewer B cells, and they are enriched for IgA-producing cells. This enhanced switch to IgA production in the absence of CLCa was attributable to increased transforming growth factor β receptor 2 (TGFβR2) signaling resulting from defective endocytosis...
August 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
Min-Min Chen, Xiao Xiao, Xiang-Ming Lao, Yuan Wei, Rui-Xian Liu, Qiu-Hui Zeng, Jun-Cheng Wang, Fang-Zhu Ouyang, Dong-Ping Chen, Ka-Wo Chan, Dai-Chao Shi, Limin Zheng, Dong-Ming Kuang
: The existence, regulation, and functions of IL21(+) immune cells are poorly defined in human cancers. Here, we identified a subset of protumorigenic IL21(+) TFH-like cells in human hepatocellular carcinoma. These cells were the major source of IL21 in tumors and represented about 10% of the CD4(+) T-cell population at levels comparable with the TFH cells present in lymph nodes. However, these TFH-like cells displayed a unique CXCR5(-)PD-1(lo/-)BTLA(-)CD69(hi) tissue-resident phenotype with substantial IFNγ production, which differed from the phenotype of TFH cells...
October 2016: Cancer Discovery
Jian Shi, Xianlin Xu, Fengbao Luo, Qianqian Shi, Xiaozhou He, Ying Xia
The aim of this study was to investigate follicular helper T (Tfh) cell response and its difference between renal graft and spleen in a rat renal transplantation model undergoing chronic allograft nephropathy (CAN). Orthotopical kidney transplantations were performed on Fischer (F344) rats and transplanted to Lewis rats, using syngeneic Lewis-Lewis grafts as controls. Tissue samples were collected at 8 weeks post-transplantation. The status of Tfh cell response was assessed by measuring the levels of transcription factor B-cell lymphoma 6 (Bcl-6), interleukin 21 (IL-21), chemokine receptor type 5 (CXCR5), and B cell activating factor belonging to the TNF family (BAFF)...
August 12, 2016: Cell Transplantation
Katherine J Nicholas, David K Flaherty, Rita M Smith, D Noah Sather, Spyros A Kalams
Peripheral CD4+CXCR5+PD-1+ T cells are a putative circulating counterpart to germinal center T follicular helper (TFH) cells. They show both phenotypic and functional similarities to TFH cells, which provide necessary help for the differentiation of B cells to antibody-secreting plasmablasts. In this study we evaluated the frequency, phenotypes, and responses of peripheral TFH-like (pTFH) cells to superantigen and recall antigen stimulation in 10 healthy and 34 chronically infected treatment-naïve HIV-1+ individuals...
August 5, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
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