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https://www.readbyqxmd.com/read/28342908/intestinal-dendritic-cell-licensing-through-tlr4-is-required-for-oral-tolerance-in-allergic-contact-dermatitis
#1
Feriel Hacini-Rachinel, Mercedes Gomez de Agüero, Reem Kanjarawi, Ludovic Moro-Sibilot, Jean-Benoit Le Luduec, Claire Macari, Gilles Boschetti, Emilie Bardel, Philippe Langella, Bertrand Dubois, Dominique Kaiserlian
BACKGROUND: Induction of oral tolerance to haptens is an efficient way to prevent allergic contact dermatitis (ACD) in mice. Toll-like receptor (TLRs)-mediated sensing of the microbiota contributes to gut homeostasis, yet whether it contributes to induction of oral tolerance has not been documented. OBJECTIVE: We examined whether oral tolerance to the contact sensitizer DNFB depends on microbiota/TLRs and evaluated the role of TLR4 on the tolerogenic function of intestinal dendritic cells (DCs)...
March 22, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28337201/phenotype-and-tissue-residency-of-lymphocytes-in-the-murine-oral-mucosa
#2
Joo-Young Park, Hyunsoo Chung, Youngnim Choi, Jung-Hyun Park
The oral mucosa is a critical barrier tissue that harbors a series of distinct immune cell subsets. Immune surveillance in the oral mucosa is important for both local and systemic immunity because the oral cavity is a heavily utilized route of pathogen entry and also serves as site of pathogen propagation. Nonetheless, composition and phenotype of the lymphocyte pool in the oral mucosa have remained poorly characterized. Utilizing a newly established protocol for mucosal immune cell isolation, here, we report that the oral mucosa features a unique cellular composition of immune cells, which differed not only from secondary lymphoid organs but also from mucosal tissues in the gut and lung...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28316599/interleukin-4-inhibits-regulatory-t-cell-differentiation-through-regulating-cd103-dendritic-cells
#3
Lei Tu, Jie Chen, Hongwei Zhang, Lihua Duan
CD103+ dendritic cells (DCs) have been shown to play a crucial role in the pathogenesis of inflammatory bowel diseases (IBDs) through educating regulatory T (Treg) cells differentiation. However, the mechanism of CD103+ DCs subsets differentiation remains elusive. Interleukin (IL)-4 is a pleiotropic cytokine that is upregulated in certain types of inflammation, including IBDs and especially ulcerative colitis. However, the precise role of IL-4 in the differentiation of CD103+ DCs subpopulation remains unknown...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28295019/m2e-tetramer-specific-memory-cd4-t-cells-are-broadly-protective-against-influenza-infection
#4
D G Eliasson, A Omokanye, K Schön, U A Wenzel, V Bernasconi, M Bemark, A Kolpe, K El Bakkouri, T Ysenbaert, L Deng, W Fiers, X Saelens, N Lycke
Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-A(d) restricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection...
March 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28286160/p2x7-receptor-promotes-intestinal-inflammation-in-chemically-induced-colitis-and-triggers-death-of-mucosal-regulatory-t-cells
#5
Vanessa R Figliuolo, Luiz Eduardo Baggio Savio, Hanaa Safya, Hayandra Nanini, Cláudio Bernardazzi, Alessandra Abalo, Heitor S P de Souza, Jean Kanellopoulos, Pierre Bobé, Cláudia M L M Coutinho, Robson Coutinho-Silva
P2X7 receptor activation contributes to inflammation development in different pathologies. We previously reported that the P2X7 receptor is over-expressed in the gut mucosa of patients with inflammatory bowel disease, and that P2X7 inhibition protects against chemically induced colitis. Here, we investigated in detail the role of the P2X7 receptor in inflammatory bowel disease development, by treating P2X7 knockout (KO) and WT mice with two different (and established) colitis inductors. P2X7 KO mice were protected against gut inflammation induced by 2,4,6-trinitrobenzenesulfonic acid or oxazolone, with no weight loss or gut histological alterations after treatment...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28276457/cd40-signalling-abrogates-induction-of-ror%C3%AE-t-treg-cells-by-intestinal-cd103-dcs-and-causes-fatal-colitis
#6
Christian Barthels, Ana Ogrinc, Verena Steyer, Stefanie Meier, Ferdinand Simon, Maria Wimmer, Andreas Blutke, Tobias Straub, Ursula Zimber-Strobl, Esther Lutgens, Peggy Marconi, Caspar Ohnmacht, Debora Garzetti, Bärbel Stecher, Thomas Brocker
Immune homeostasis in intestinal tissues depends on the generation of regulatory T (Treg) cells. CD103(+) dendritic cells (DCs) acquire microbiota-derived material from the gut lumen for transport to draining lymph nodes and generation of receptor-related orphan γt(+) (RORγt(+)) Helios(-)-induced Treg (iTreg) cells. Here we show CD40-signalling as a microbe-independent signal that can induce migration of CD103(+) DCs from the lamina propria (LP) to the mesenteric lymph nodes. Transgenic mice with constitutive CD11c-specific CD40-signalling have reduced numbers of CD103(+) DCs in LP and a low frequency of RORγt(+)Helios(-) iTreg cells, exacerbated inflammatory Th1/Th17 responses, high titres of microbiota-specific immunoglobulins, dysbiosis and fatal colitis, but no pathology is detected in other tissues...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28262752/highly-exposed-hiv-1-seronegative-female-commercial-sex-workers-sustain-in-their-genital-mucosa-increased-frequencies-of-tolerogenic-myeloid-and-regulatory-t-cells
#7
V Thibodeau, L Fourcade, A-C Labbé, M Alary, F Guédou, J Poudrier, M Roger
We and others have shown that HIV-1 highly-exposed seronegative (HESN) female commercial sex workers (CSWs) maintain low genital inflammatory conditions to prevent HIV infection. HIV-1 interacts with toll-like receptors (TLR)-7/8 to induce interferon (IFN)-α, an important antiviral and immunomodulatory cytokine, which act together with interleukin (IL)-10, human leukocyte antigen (HLA)-G and immunoglobulin-like transcript (ILT)-4 to initiate a "tolerogenic/regulatory" anti-inflammatory loop. In view of further unravelling elements associated with natural immunity to HIV-1, we have characterised TLR-7, IFN-α, IL-10, HLA-G and ILT-4 expression profiles in the genital tract of female CSWs and HIV-1-uninfected non-CSWs from Benin...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261866/morphologic-and-immunophenotypic-features-of-hairy-cell-leukemia-involving-lymph-nodes-and-extranodal-tissues
#8
Jacqueline M Cortazar, Daniel J DeAngelo, Geraldine S Pinkus, Elizabeth A Morgan
Hairy cell leukemia (HCL) is a rare B-cell neoplasm that mainly affects bone marrow (BM), peripheral blood (PB), and spleen. Involvement of lymph nodes and extranodal structures is considered infrequent. Herein we describe our institutional experience of nodal (n=10) and extranodal (n=3) HCL over a thirty-year period. Ten patients had prior evidence of HCL within the BM or PB at a median 35.8 months before nodal/extranodal diagnosis (range, <1 to 175 months), and HCL was diagnosed concurrently within the bone marrow of 1 additional patient...
March 6, 2017: Histopathology
https://www.readbyqxmd.com/read/28261667/protein-malnutrition-modifies-innate-immunity-and-gene-expression-by-intestinal-epithelial-cells-and-human-rotavirus-infection-in-neonatal-gnotobiotic-pigs
#9
Anastasia N Vlasova, Francine C Paim, Sukumar Kandasamy, Moyasar A Alhamo, David D Fischer, Stephanie N Langel, Loic Deblais, Anand Kumar, Juliet Chepngeno, Lulu Shao, Huang-Chi Huang, Rosario A Candelero-Rueda, Gireesh Rajashekara, Linda J Saif
Malnutrition affects millions of children in developing countries, compromising immunity and contributing to increased rates of death from infectious diseases. Rotavirus is a major etiological agent of childhood diarrhea in developing countries, where malnutrition is prevalent. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. In this study, we used neonatal gnotobiotic (Gn) pigs transplanted with the fecal microbiota of a healthy 2-month-old infant (HIFM) and fed protein-deficient or -sufficient bovine milk diets...
March 2017: MSphere
https://www.readbyqxmd.com/read/28261212/%C3%AE-2%C3%A2-1-fructans-modulate-the-immune-system-in-vivo-in-a-microbiota-dependent-and%C3%A2-independent-fashion
#10
Floris Fransen, Neha M Sahasrabudhe, Marlies Elderman, Margaret Bosveld, Sahar El Aidy, Floor Hugenholtz, Theo Borghuis, Ben Kousemaker, Simon Winkel, Christa van der Gaast-de Jongh, Marien I de Jonge, Mark V Boekschoten, Hauke Smidt, Henk A Schols, Paul de Vos
It has been shown in vitro that only specific dietary fibers contribute to immunity, but studies in vivo are not conclusive. Here, we investigated degree of polymerization (DP) dependent effects of β2→1-fructans on immunity via microbiota-dependent and -independent effects. To this end, conventional or germ-free mice received short- or long-chain β2→1-fructan for 5 days. Immune cell populations in the spleen, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs) were analyzed with flow cytometry, genome-wide gene expression in the ileum was measured with microarray, and gut microbiota composition was analyzed with 16S rRNA sequencing of fecal samples...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28256637/ebola-virus-infection-kinetics-in-chimeric-mice-reveal-a-key-role-of-t-cells-as-barriers-for-virus-dissemination
#11
Anja Lüdtke, Paula Ruibal, David M Wozniak, Elisa Pallasch, Stephanie Wurr, Sabrina Bockholt, Sergio Gómez-Medina, Xiangguo Qiu, Gary P Kobinger, Estefanía Rodríguez, Stephan Günther, Susanne Krasemann, Juliana Idoyaga, Lisa Oestereich, César Muñoz-Fontela
Ebola virus (EBOV) causes severe systemic disease in humans and non-human primates characterized by high levels of viremia and virus titers in peripheral organs. The natural portals of virus entry are the mucosal surfaces and the skin where macrophages and dendritic cells (DCs) are primary EBOV targets. Due to the migratory properties of DCs, EBOV infection of these cells has been proposed as a necessary step for virus dissemination via draining lymph nodes and blood. Here we utilize chimeric mice with competent hematopoietic-driven immunity, to show that EBOV primarily infects CD11b(+) DCs in non-lymphoid and lymphoid tissues, but spares the main cross-presenting CD103(+) DC subset...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28231307/differential-regulation-of-c5a-receptor-1-in-innate-immune-cells-during-the-allergic-asthma-effector-phase
#12
Fanny Ender, Anna V Wiese, Inken Schmudde, Jing Sun, Tillman Vollbrandt, Peter König, Yves Laumonnier, Jörg Köhl
C5a drives airway constriction and inflammation during the effector phase of allergic asthma, mainly through the activation of C5a receptor 1 (C5aR1). Yet, C5aR1 expression on myeloid and lymphoid cells during the allergic effector phase is ill-defined. Recently, we generated and characterized a floxed green fluorescent protein (GFP)-C5aR1 knock-in mouse. Here, we used this reporter strain to monitor C5aR1 expression in airway, pulmonary and lymph node cells during the effector phase of OVA-driven allergic asthma...
2017: PloS One
https://www.readbyqxmd.com/read/28212742/demonstration-of-tissue-resident-memory-cd8-t-cells-in-insulitic-lesions-in-adult-patients-with-recent-onset-type-1-diabetes
#13
Enida Kuric, Peter Seiron, Lars Krogvold, Bjørn Edwin, Trond Buanes, Kristian F Hanssen, Oskar Skog, Knut Dahl-Jørgensen, Olle Korsgren
Subtypes of CD8(+) T cells in insulitic lesions in biopsy specimens from six subjects with recent-onset type 1 diabetes (T1D) and six nondiabetic matched controls were analyzed using simultaneous multicolor immunofluorescence. Also, insulitic islets based on accumulation of CD3(+) T cells were microdissected with laser-capture microscopy, and gene transcripts associated with inflammation and autoimmunity were analyzed. We found a substantial proportion, 43%, of the CD8(+) T cells in the insulitic lesions to display a tissue resident memory T cell (TRM) (CD8(+)CD69(+)CD103(+)) phenotype in T1D subjects...
March 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28198365/development-of-conventional-dendritic-cells-from-common-bone-marrow-progenitors-to-multiple-subsets-in-peripheral-tissues
#14
REVIEW
D Sichien, B N Lambrecht, M Guilliams, C L Scott
Our understanding of conventional dendritic cell (cDC) development and the functional specializations of distinct subsets in the peripheral tissues has increased greatly in recent years. Here, we review cDC development from the distinct progenitors in the bone marrow through to the distinct cDC subsets found in barrier tissues, providing an overview of the different subsets described in each location. In addition, we detail the transcription factors and local signals that have been proposed to control this developmental process...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28194020/cd103-lung-dendritic-cells-ldcs-induce-stronger-th1-th17-immunity-to-a-bacterial-lung-infection-than-cd11b-hi-ldcs
#15
Sudhanshu Shekhar, Ying Peng, Shuhe Wang, Xi Yang
Recent studies suggest differential roles for CD103+ and CD11b(hi) lung dendritic cells (LDCs) in host defense against viral and bacterial infections. In this study, we examined the contribution of these LDC subsets in protective immunity to chlamydial lung infection using a Chlamydia muridarum mouse infection model. We found that CD103+ LDCs showed higher expression of costimulatory molecules (CD40, CD80 and CD86) and increased production of cytokines (IL-12p70, IL-10, IL-23 and IL-6) compared with CD11b(hi) LDCs, but the expression of programmed death-ligand 1 (PD-L1) was similar between the two subsets...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28167776/tgf-%C3%AE-inhibitor-smad7-regulates-dendritic-cell-induced-autoimmunity
#16
Dominika Lukas, Nir Yogev, Junda M Kel, Tommy Regen, Ilgiz A Mufazalov, Yilang Tang, Florian Wanke, Boris Reizis, Werner Müller, Florian C Kurschus, Marco Prinz, Ingo Kleiter, Björn E Clausen, Ari Waisman
TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8(+)CD103(+) DCs in the spleen. Furthermore, Smad7-deficient DCs expressed higher levels of indoleamine 2,3-dioxygenase (IDO), an enzyme associated with tolerance induction...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28164171/diminished-cd103-%C3%AE-e%C3%AE-7-expression-on-resident-t-cells-from-the-female-genital-tract-of-hiv-positive-women
#17
David C Moylan, Paul A Goepfert, Mirjam-Colette Kempf, Michael S Saag, Holly E Richter, Jiri Mestecky, Steffanie Sabbaj
BACKGROUND: Tissue resident memory T cells (TrM) provide an enhanced response against infection at mucosal surfaces, yet their function has not been extensively studied in humans, including the female genital tract (FGT). METHODS: Using polychromatic flow cytometry, we studied TrM cells, defined as CD62L-CCR7-CD103(+)CD69(+) CD4(+) and CD8(+) T cells in mucosa-derived T cells from healthy and HIV-positive women. RESULTS: We demonstrate that TrM are present in the FGT of healthy and HIV-positive women...
October 2016: Pathogens & Immunity
https://www.readbyqxmd.com/read/28152503/the-prognostic-value-of-tumor-infiltrating-t-lymphocytes-in-ovarian-cancer
#18
Jun Li, Jieyu Wang, Ruifang Chen, Yang Bai, Xin Lu
The prognostic value of tumor-infiltrating lymphocytes (TILs) in ovarian cancer is still in controversial. This study is aimed to assess the impact of different TIL subsets on the progression free survival (PFS)/disease free survival (DSS) and overall survival (OS)/disease specific survival (DSS) in ovarian cancer. A comprehensive literature search in PubMed, ISI Web of Science, and Medline was performed to identify relevant studies evaluating the prognostic value of TILs in ovarian cancer. Reviews of each study were conducted and data were extracted...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28140445/virulence-dependent-induction-of-interleukin-10-producing-tolerogenic-dendritic-cells-by-mycobacterium-tuberculosis-impedes-optimal-th1-proliferation
#19
Hongmin Kim, Kee Woong Kwon, Woo Sik Kim, Sung Jae Shin
Mycobacterium tuberculosis (Mtb) inhibits optimal Th1 responses during infection. However, the precise mechanisms by which virulent Mtb limits Th1 responses remain unclear. Here, we infected dendritic cells (DCs) with the virulent Mtb strain H37Rv or the attenuated strain H37Ra to investigate the phenotypic and functional alterations in DCs and resultant T cell responses. H37Rv-infected DCs suppressed Th1 responses more strongly than H37Ra-infected DCs. Interestingly, H37Rv, but not H37Ra, impaired DC surface molecule (CD80, CD86 and MHC class II) expression due to prominent IL-10 production while augmenting the expression of tolerogenic molecules including PD-L1, CD103, Tim-3, and indoleamine 2,3-dioxygenase (IDO) on DCs in a multiplicity-of-infection-dependent manner...
January 31, 2017: Immunology
https://www.readbyqxmd.com/read/28112260/an-altered-endometrial-cd8-tissue-resident-memory-t-cell-population-in-recurrent-miscarriage
#20
J H Southcombe, G Mounce, K McGee, A Elghajiji, J Brosens, S Quenby, T Child, I Granne
When trying to conceive 1% of couples have recurrent miscarriages, defined as three or more consecutive pregnancy losses. This is not accounted for by the known incidence of chromosomal aneuploidy in miscarriage, and it has been suggested that there is an immunological aetiology. The endometrial mucosa is populated by a variety of immune cells which in addition to providing host pathogen immunity must facilitate pregnancy. Here we characterise the endometrial CD8-T cell population during the embryonic window of implantation and find that the majority of cells are tissue resident memory T cells with high levels of CD69 and CD103 expression, proteins that prevent cells egress...
January 23, 2017: Scientific Reports
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