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Joern Pezoldt, Jochen Huehn
Upon differentiation, T cells acquire tissue-specific homing properties allowing efficient targeting of effector T cells into distinct inflamed organs. Priming of T cells within skin-draining, peripheral lymph nodes (pLNs) leads to the expression of E- and P-selectin ligands, which facilitate migration into inflamed skin, whereas activation within gut-draining, mesenteric LNs (mLNs) results in induction of chemokine receptor CCR9 and integrin α4β7, both required for migration of effector T cells into mucosal tissues...
September 29, 2016: European Journal of Microbiology & Immunology
Lisa S Thomas, Stephan R Targan, Masato Tsuda, Qi T Yu, Brenda C Salumbides, Talin Haritunians, Emebet Mengesha, Dermot P B McGovern, Kathrin S Michelsen
TL1A contributes to the pathogenesis of several chronic inflammatory diseases, including those of the bowel by enhancing TH1, TH17, and TH2 responses. TL1A mediates a strong costimulation of these TH subsets, particularly of mucosal CCR9(+) T cells. However, the signaling pathways that TL1A induces in different TH subsets are incompletely understood. We investigated the function of TL1A on human TH17 cells. TL1A, together with TGF-β, IL-6, and IL-23, enhanced the secretion of IL-17 and IFN-γ from human CD4(+) memory T cells...
October 12, 2016: Journal of Leukocyte Biology
Takeru Amiya, Nobuhiro Nakamoto, Po-Sung Chu, Toshiaki Teratani, Hideaki Nakajima, Yumi Fukuchi, Nobuhito Taniki, Akihiro Yamaguchi, Shunsuke Shiba, Rei Miyake, Tadashi Katayama, Hirotoshi Ebinuma, Takanori Kanai
The fundamental mechanism how heterogeneous hepatic macrophage (Mφ) subsets fulfill diverse functions in health and disease has not been elucidated. We recently reported that CCR9(+) inflammatory Mφs play a critical role in the course of acute liver injury. To clarify the origin and differentiation of CCR9(+)Mφs, we used a unique partial bone marrow (BM) chimera model with liver shielding for maintaining hepatic resident Mφs. First, irradiated mice developed less liver injury with less Mφs accumulation by Concanavalin A (Con A) regardless of liver shielding...
October 11, 2016: Scientific Reports
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
Mats Bemark, Helena Hazanov, Anneli Strömberg, Rathan Komban, Joel Holmqvist, Sofia Köster, Johan Mattsson, Per Sikora, Ramit Mehr, Nils Y Lycke
Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8(high)/GFP(+) NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured...
2016: Nature Communications
Lei Wang, Xiaohuan Wang, Kuo Bi, Ximeng Sun, Jing Yang, Yuan Gu, Jingjing Huang, Bin Zhan, Xinping Zhu
BACKGROUND: Our previous studies showed that Trichinella spiralis paramyosin (TsPmy) is an immunomodulatory protein that inhibits complement C1q and C8/C9 to evade host complement attack. Vaccination with recombinant TsPmy protein induced protective immunity against T. spiralis larval challenge. Due to the difficulty in producing TsPmy as a soluble recombinant protein, we prepared a DNA vaccine as an alternative approach in order to elicit a robust immunity against Trichinella infection...
September 2016: PLoS Neglected Tropical Diseases
Yan Huang, Dandan Wang, Xin Wang, Yijie Zhang, Tao Liu, Yuting Chen, Yanhong Tang, Teng Wang, Dan Hu, Congxin Huang
CC chemokine receptor 9 (CCR9), which is a unique receptor for CC chemokine ligand (CCL25), is mainly expressed on lymphocytes, dendritic cells (DCs) and monocytes/macrophages. CCR9 mediates the chemotaxis of inflammatory cells and participates in the pathological progression of inflammatory diseases. However, the role of CCR9 in the pathological process of myocardial infarction (MI) remains unexplored; inflammation plays a key role in this process. Here, we used CCR9 knockout mice to determine the functional significance of CCR9 in regulating post-MI cardiac remodeling and its underlying mechanism...
2016: Scientific Reports
Vivian Zhou, Kimberle Agle, Xiao Chen, Amy Beres, Richard Komorowski, Ludovic Belle, Carolyn Taylor, Fenlu Zhu, Dipica Haribhai, Calvin B Williams, James Verbsky, Wendy Blumenschein, Svetlana Sadekova, Eddie Bowman, Christie Ballantyne, Casey Weaver, David A Serody, Benjamin Vincent, Jonathan Serody, Daniel J Cua, William R Drobyski
Damage to the gastrointestinal tract is a major cause of morbidity and mortality in graft-versus-host disease (GVHD) and is attributable to T cell-mediated inflammation. In this work, we identified a unique CD4+ T cell population that constitutively expresses the β2 integrin CD11c and displays a biased central memory phenotype and memory T cell transcriptional profile, innate-like properties, and increased expression of the gut-homing molecules α4β7 and CCR9. Using several complementary murine GVHD models, we determined that adoptive transfer and early accumulation of β2 integrin-expressing CD4+ T cells in the gastrointestinal tract initiated Th1-mediated proinflammatory cytokine production, augmented pathological damage in the colon, and increased mortality...
September 1, 2016: Journal of Clinical Investigation
Ashley C Mays, Xin Feng, James D Browne, Christopher A Sullivan
AIM: To characterize the chemokine pattern in metastatic salivary adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: Real-time polymerase chain reaction (RT-PCR) was used to compare chemokine and chemokine receptor gene expression in two SACC cell lines: SACC-83 and SACC-LM (lung metastasis). Chemokines and receptor genes were then screened and their expression pattern characterized in human tissue samples of non-recurrent SACC and recurrent SACC with perineural invasion...
August 2016: Anticancer Research
Dominic P Golec, Laura M Henao Caviedes, Troy A Baldwin
T cell development is dependent on the migration of progenitor cells from the bone marrow to the thymus. Upon reaching the thymus, progenitors undergo a complex developmental program that requires inputs from various highly conserved signaling pathways including the Notch and Wnt pathways. To date, Ras signaling has not been implicated in the very earliest stages of T cell differentiation, but members of a family of Ras activators called RasGRPs have been shown to be involved at multiple stages of T cell development...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Inna G Ovsyannikova, Ann L Oberg, Richard B Kennedy, Michael T Zimmermann, Iana H Haralambieva, Krista M Goergen, Diane E Grill, Gregory A Poland
To assess gene signatures related to humoral response among healthy older subjects following seasonal influenza vaccination, we studied 94 healthy adults (50-74 years old) who received one documented dose of licensed trivalent influenza vaccine containing the A/California/7/2009 (H1N1)-like virus strain. Influenza-specific antibody (HAI) titer in serum samples and next-generation sequencing on PBMCs were performed using blood samples collected prior to (Day 0) and at two timepoints after (Days 3 and 28) vaccination...
May 2016: Heliyon
Yaxian Kong, Yajie Li, Weimei Zhang, Shaoxin Yuan, René Winkler, Ulrike Kröhnert, Junyan Han, Tao Lin, Yu Zhou, Peng Miao, Beibei Wang, Jianping Zhang, Zhengya Yu, Yu Zhang, Christian Kosan, Hui Zeng
Impaired T lymphopoiesis is associated with immunosuppression of the adaptive immune response and plays a role in the morbidity and mortality of patients and animal models of sepsis. Although previous studies examined several intrathymic mechanisms that negatively affect T lymphopoiesis, the extrathymic mechanisms remain poorly understood. Here, we report a dramatic decrease in the percentage of early T lineage progenitors (ETPs) in three models of sepsis in mice (cecal ligation and puncture, lipopolysaccharide continuous injection, and poly I:C continuous injection)...
July 16, 2016: Stem Cells
Leo C Chen, Yawah T Nicholson, Brian R Rosborough, Angus W Thomson, Giorgio Raimondi
The vitamin A metabolite all-trans retinoic acid (ATRA) induces a gut-homing phenotype in activated CD4(+) conventional T cells (Tconv) by upregulating the integrin α4β7 and the chemokine receptor CCR9. We report that, in contrast to mouse Tconv, only ∼50% of regulatory T cells (Treg) upregulate CCR9 when stimulated by physiological levels of ATRA, even though Tconv and Treg express similar levels of the retinoic acid receptor (RAR). The resulting bimodal CCR9 expression is not associated with differences in the extent of their proliferation, level of Foxp3 expression, or affiliation with naturally occurring Treg or induced Treg in the circulating Treg pool...
August 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Toshihiro Nanki
  Chemokines induce migration of inflammatory cells. In the synovial tissue of rheumatoid arthritis (RA), abundant chemokines are expressed, which contribute migration of lymphocytes and monocytes/macrophages, stimulation of synovial cells, and angiogenesis. Blockade of CCL2, CCL3, CCL5, CCR1, CCR9, CXCL2, CXCL5, CXCL13, CXCL16, CXCR3, CXCR4, CXCR7, and CX3CL1 showed improvement of arthritis of animal models. Moreover, CCR1 antagonist and anti-CXCL10 antibody reduced arthritis of patients with RA. Chemokine is a promising target for RA therapy...
2016: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
Alexandre Girard, Delphine Vergnon-Miszczycha, Anne-Emmanuelle Depincé-Berger, Xavier Roblin, Frederic Lutch, Claude Lambert, Nicolas Rochereau, Thomas Bourlet, Christian Genin, Stéphane Paul
OBJECTIVE: Correlation between GALT homing markers on lymphocytes and the low blood CD4 T-cell reconstitution in immunological nonresponders (INRs) has been studied. DESIGN: Thirty-one INRs, 19 immunological responders (IRs), and 12 noninfected controls were enrolled in this study. INRs were defined by an undetectable plasma viral load RNA less than 40 copies per milliliter and CD4 T-cell count <500 cells per cubic milliliter in at least 3 years. METHODS: A complete peripheral and mucosal lymphocyte immunophenotyping was performed on these patients with a focus on the CCR9, CCR6, and α4β7 gut-homing markers...
July 1, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Allison Cabinian, Daniel Sinsimer, May Tang, Osvaldo Zumba, Hetali Mehta, Annmarie Toma, Derek Sant'Angelo, Yasmina Laouar, Amale Laouar
Despite our knowledge of the protective role of antibodies passed to infants through breast milk, our understanding of immunity transfer via maternal leukocytes is still limited. To emulate the immunological interface between the mother and her infant while breast-feeding, we used murine pups fostered after birth onto MHC-matched and MHC-mismatched dams. Overall, data revealed that: 1) Survival of breast milk leukocytes in suckling infants is possible, but not significant after the foster-nursing ceases; 2) Most breast milk lymphocytes establish themselves in specific areas of the intestine termed Peyer's patches (PPs); 3) While most leukocytes in the milk bolus were myeloid cells, the majority of breast milk leukocytes localized to PPs were T lymphocytes, and cytotoxic T cells (CTLs) in particular; 4) These CTLs exhibit high levels of the gut-homing molecules α4β7 and CCR9, but a reduced expression of the systemic homing marker CD62L; 5) Under the same activation conditions, transferred CD8 T cells through breast milk have a superior capacity to produce potent cytolytic and inflammatory mediators when compared to those generated by the breastfed infant...
2016: PloS One
Bhaumik A Pandya, Christian Baber, Audrey Chan, Brian Chamberlain, Haoqun Chandonnet, Jennifer Goss, Timothy Hopper, Blaise Lippa, Katherine Poutsiaka, Jan Romero, Sabrina Stucka, Mustafa Varoglu, Jing Zhang, Xin Zhang
Irritable bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC) are serious chronic diseases affecting millions of patients worldwide. Studies of human chemokine biology has suggested C-C chemokine receptor 9 (CCR9) may be a key mediator of pro-inflammatory signaling. Discovery of agents that inhibit CCR9 may lead to new therapies for CD and UC patients. Herein we describe the evolution of a high content screening hit (1) into potent inhibitors of CCR9, such as azaindole 12.
July 15, 2016: Bioorganic & Medicinal Chemistry Letters
Julie Gauvin, Josiane Chagnon-Choquet, Johanne Poudrier, Michel Roger
We have previously shown that overexpression of BLyS/BAFF was associated with increased relative frequencies of innate "precursor" marginal zone (MZ)-like B-cells in the blood of HIV-1-infected rapid and classic progressors. However, along with relatively normal BLyS/BAFF expression levels, these cells remain unaltered in elite-controllers (EC), rather, percentages of more mature MZ-like B-cells are decreased in the blood of these individuals. Fluctuations in frequencies of blood MZ-like B-cell populations may reflect migratory patterns associated with disease progression status, suggesting an important role for these cells in HIV-1 pathogenesis...
2016: PloS One
Jens Bauer, Regine J Dress, Anja Schulze, Philipp Dresing, Shafaqat Ali, René Deenen, Judith Alferink, Stefanie Scheu
Type I IFNs are critical in initiating protective antiviral immune responses, and plasmacytoid dendritic cells (pDCs) represent a major source of these cytokines. We show that only few pDCs are capable of producing IFN-β after virus infection or CpG stimulation. Using IFNβ/YFP reporter mice, we identify these IFN-β-producing cells in the spleen as a CCR9(+)CD9(-) pDC subset that is localized exclusively within the T/B cell zones. IFN-β-producing pDCs exhibit a distinct transcriptome profile, with higher expression of genes encoding cytokines and chemokines, facilitating T cell recruitment and activation...
June 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Jeong-Bin Ahn, Shin Ae Kang, Dong-Hee Kim, Hak Sun Yu
As most infections by the helminth parasite elicit the recruitment of CD4(+)CD25(+)Foxp3(+) T (Treg) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated Treg cells, we compared the expression levels of Treg cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of Treg cells was monitored using GFP-coded Foxp3 transgenic mice...
April 2016: Korean Journal of Parasitology
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