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https://www.readbyqxmd.com/read/27905296/a-pathogenic-role-for-the-integrin-cd103-in-experimental-allergic-airways-disease
#1
Vanessa S Fear, Siew Ping Lai, Graeme R Zosky, Kara L Perks, Shelley Gorman, Fabian Blank, Christophe von Garnier, Philip A Stumbles, Deborah H Strickland
The integrin CD103 is the αE chain of integrin αEβ7 that is important in the maintenance of intraepithelial lymphocytes and recruitment of T cells and dendritic cells (DC) to mucosal surfaces. The role of CD103 in intestinal immune homeostasis has been well described, however, its role in allergic airway inflammation is less well understood. In this study, we used an ovalbumin (OVA)-induced, CD103-knockout (KO) BALB/c mouse model of experimental allergic airways disease (EAAD) to investigate the role of CD103 in disease expression, CD4(+) T-cell activation and DC activation and function in airways and lymph nodes...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27903738/tgf-%C3%AE-controls-the-formation-of-kidney-resident-t-cells-via-promoting-effector-t-cell-extravasation
#2
Chaoyu Ma, Shruti Mishra, Erika L Demel, Yong Liu, Nu Zhang
Tissue-resident memory T (TRM) cells, a population of noncirculating memory T cells, are one of the essential components of immunological memory in both mouse and human. Although CD69(+)CD103(+) TRM cells represent a major TRM cell population in barrier tissues including the mucosal surface and the skin, CD69(+)CD103(-) TRM cells dominate most nonbarrier tissues, such as the kidney. TGF-β is required for the differentiation of CD69(+)CD103(+) TRM cells in barrier tissues. However, the developmental control of CD69(+)CD103(-) TRM cells in nonbarrier tissues remains largely unknown and the involvement of TGF-β signaling is less clear...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27899443/rab43-facilitates-cross-presentation-of-cell-associated-antigens-by-cd8%C3%AE-dendritic-cells
#3
Nicole M Kretzer, Derek J Theisen, Roxane Tussiwand, Carlos G Briseño, Gary E Grajales-Reyes, Xiaodi Wu, Vivek Durai, Jörn Albring, Prachi Bagadia, Theresa L Murphy, Kenneth M Murphy
In this study, to examine cross-presentation by classical dendritic cells (DCs; cDCs), we evaluated the role of RAB43, a protein found to be selectively expressed by Batf3-dependent CD8α(+) and CD103(+) compared with other DC subsets and immune lineages. Using a specific monoclonal antibody, we localized RAB43 expression to the Golgi apparatus and LAMP1(-) cytoplasmic vesicles. Mice with germline or conditional deletion of Rab43 are viable and fertile and have normal development of cDCs but show a defect for in vivo and in vitro cross-presentation of cell-associated antigen...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27897208/beta-1-integrin-ligation-and-tlr-ligation-enhance-gm-csf-induced-aldh1a2-expression-in-dendritic-cells-but-differentially-regulate-their-anti-inflammatory-properties
#4
Aya Yokota-Nakatsuma, Yoshiharu Ohoka, Hajime Takeuchi, Si-Young Song, Makoto Iwata
Retinoic acid (RA)-producing CD103(+) mature dendritic cells (DCs) in mesenteric lymph nodes (MLNs) play crucial roles in gut immunity. GM-CSF and RA contribute to the expression of the RA-producing enzyme ALDH1A2. However, additional signals appeared to be required for inducing ALDH1A2(high) mature DCs from immature DCs. We found here that TLR ligands (Ls) and immobilized E-cadherin could provide such signals in FLT3-L-generated bone marrow (BM)-derived DCs after treatment with GM-CSF and the RA receptor agonist Am80...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27897162/batf3-selectively-determines-acquisition-of-cd8-dendritic-cell-phenotype-and-function
#5
Janin Chandra, Paula T Y Kuo, Anne M Hahn, Gabrielle T Belz, Ian H Frazer
Batf3 is a transcription factor that impacts the development of CD103(+) tissue-resident dendritic cells (DCs). However, whether Batf3 is absolutely required for the development of CD8(+) DCs remains controversial. Id2 is required for CD8(+) DC development. Here we show that bone marrow chimeric mice with a deletion of Id2 in the CD11c compartment lose the ability to reject a skin graft expressing a non-self protein antigen or mount a delayed hypersensitivity response. In contrast, Batf3((-/-)) mice remained competent for skin graft rejection and delayed hypersensitivity, and retained a CD8(+) DC population with markers characteristic of the CD11b(+) DC lineage, including CD11b, CD4 and CD172α, as well as the key regulator transcription factor IRF4, but lacked IRF8 expression...
November 29, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27895172/pulmonary-dendritic-cell-subsets-shape-the-respiratory-syncytial-virus-specific-cd8-t-cell-immunodominance-hierarchy-in-neonates
#6
Allison M W Malloy, Tracy J Ruckwardt, Kaitlyn M Morabito, Annie W Lau-Kilby, Barney S Graham
Young infants are generally more susceptible to viral infections and experience more severe disease than do adults. CD8(+) T cells are important for viral clearance, and although often ineffective in neonates they can be protective when adequately stimulated. Using a murine CB6F1/J hybrid model of respiratory syncytial virus (RSV) infection, we previously demonstrated that the CD8(+) T cell immunodominance hierarchy to two RSV-derived epitopes, K(d)M282-90 and D(b)M187-195, was determined by the age at infection...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27864475/il-17-producing-innate-and-pathogen-specific-tissue-resident-memory-%C3%AE-%C3%AE-t-cells-expand-in-the-lungs-of-bordetella-pertussis-infected-mice
#7
Alicja Misiak, Mieszko M Wilk, Mathilde Raverdeau, Kingston H G Mills
γδ T cells play a role in protective immunity to infection at mucosal surface, but also mediate pathology in certain autoimmune diseases through innate IL-17 production. Recent reports have suggested that γδ T cells can have memory analogous to conventional αβ T cells. In this study we have examined the role of γδ T cells in immunity to the respiratory pathogen Bordetella pertussis γδ T cells, predominantly Vγ4(-)γ1(-) cells, produced IL-17 in the lungs as early as 2 h after infection. The bacterial burden during primary infection was significantly enhanced and the induction of antimicrobial peptides was reduced in the absence of early IL-17...
November 18, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27861804/cd103-cd11b-salivary-gland-dendritic-cells-have-antigen-cross-presenting-capacity
#8
Lu Lu, Yukinori Tanaka, Naoto Ishii, Takashi Sasano, Shunji Sugawara
Dendritic cells (DCs) in lymphoid and non-lymphoid tissues are professional antigen-presenting cells that are essential for effective immunity and tolerance. However, the presence and characteristics of DCs in steady-state salivary glands (SGs) currently remain unknown. We herein identified CD64(-) CD11c(+) classical DCs (cDCs) as well as CD64(+) macrophages among CD45(+) MHC class II(+) antigen-presenting cells in steady-state murine SGs. SG cDCs were divided into CD103(+) CD11b(-) and CD103(-) CD11b(+) cDCs...
November 11, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27852745/dectin-1-plays-an-important-role-in-house-dust-mite-induced-allergic-airway-inflammation-through-the-activation-of-cd11b-dendritic-cells
#9
Takashi Ito, Koichi Hirose, Ayako Norimoto, Tomohiro Tamachi, Masaya Yokota, Aiko Saku, Hiroaki Takatori, Shinobu Saijo, Yoichiro Iwakura, Hiroshi Nakajima
It is well known that sensitization against fungi is closely associated with severity of asthma. Dectin-1 (gene symbol Clec7a), a C-type lectin receptor, recognizes the fungal cell wall component β-glucan, as well as some component(s) in house dust mite (HDM) extract. However, the roles of Dectin-1 in HDM-induced allergic airway inflammation remain unclear. In this study, we used Dectin-1-deficient (Clec7a(-/-)) mice to examine whether Dectin-1 is involved in HDM-induced allergic airway inflammation. We found that HDM-induced eosinophil and neutrophil recruitment into the airways was significantly attenuated in Clec7a(-/-) mice compared with that in wild-type mice...
November 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27834952/double-stranded-rna-promotes-ctl-independent-tumor-cytolysis-mediated-by-cd11b-ly6g-intratumor-myeloid-cells-through-the-ticam-1-signaling-pathway
#10
Hiroaki Shime, Misako Matsumoto, Tsukasa Seya
PolyI:C, a synthetic double-stranded RNA analog, acts as an immune-enhancing adjuvant that regresses tumors in cytotoxic T lymphocyte (CTL)-dependent and CTL-independent manner, the latter of which remains largely unknown. Tumors contain CD11b(+)Ly6G(+) cells, known as granulocytic myeloid-derived suppressor cells (G-MDSCs) or tumor-associated neutrophils (TANs) that play a critical role in tumor progression and development. Here, we demonstrate that CD11b(+)Ly6G(+) cells respond to polyI:C and exhibit tumoricidal activity in an EL4 tumor implant model...
November 11, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27825459/origin-of-waldenstrom-s-macroglobulinaemia
#11
REVIEW
Ramón García-Sanz, Cristina Jiménez, Noemí Puig, Bruno Paiva, Norma C Gutiérrez, Paula Rodríguez-Otero, Julia Almeida, Jesús San Miguel, Alberto Orfão, Marcos González, Martín Pérez-Andrés
Waldenstrom's macroglobulinaemia (WM) is an MYD88(L265P)-mutated lymphoplasmacytic lymphoma that invades bone marrow and secretes monoclonal immunoglobulin M (IgM). WM cells are usually unable to undergo class switch recombination, and have mutated IGHV, with a typical immunophenotype CD19(+)/CD22(low+)/CD23(-)/CD25(+)/CD27(+)/CD45(+)/CD38(low+)/SmIgM(+) (negative for CD5, CD10, CD11c, CD103). This immunophenotype matches memory B cells (smIgM(-/+)/CD10(-)/CD19(+)/CD20(+)/CD27(+)/CD38(low+)/CD45(+)), representing 30% of B cells in the blood...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27822211/cd4-t-follicular-helper-and-iga-b-cell-numbers-in-gut-biopsies-from-hiv-infected-subjects-on-antiretroviral-therapy-are-similar-to-hiv-uninfected-individuals
#12
John Zaunders, Mark Danta, Michelle Bailey, Gerald Mak, Katherine Marks, Nabila Seddiki, Yin Xu, David J Templeton, David A Cooper, Mark A Boyd, Anthony D Kelleher, Kersten K Koelsch
BACKGROUND: Disruption of gastrointestinal tract epithelial and immune barriers contribute to microbial translocation, systemic inflammation, and progression of HIV-1 infection. Antiretroviral therapy (ART) may lead to reconstitution of CD4(+) T cells in gut-associated lymphoid tissue (GALT), but its impact on humoral immunity within GALT is unclear. Therefore, we studied CD4(+) subsets, including T follicular helper cells (Tfh), as well as resident B cells that have switched to IgA production, in gut biopsies, from HIV(+) subjects on suppressive ART compared to HIV-negative controls (HNC)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27820700/the-transcription-factor-nr4a3-controls-cd103-dendritic-cell-migration
#13
Kiwon Park, Zbigniew Mikulski, Goo-Young Seo, Aleksander Y Andreyev, Paola Marcovecchio, Amy Blatchley, Mitchell Kronenberg, Catherine C Hedrick
The transcription factor NR4A3 (also known as NOR-1) is a member of the Nr4a family of nuclear receptors and is expressed in myeloid and lymphoid cells. Here, we have shown that Nr4a3 is essential for the migration of CD103+ dendritic cells (DCs) to lymph nodes (LNs). Nr4a3-deficient mice had very few CD103+ migratory DCs (mDCs) present in LNs, and mixed-chimera studies revealed that this migratory defect was cell intrinsic. We further found that CD103+ DCs from Nr4a3-deficient mice displayed a marked loss of surface expression of the chemokine CCR7...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27803187/exogenous-activation-of-invariant-natural-killer-t-cells-by-%C3%AE-galactosylceramide-reduces-pneumococcal-outgrowth-and-dissemination-postinfluenza
#14
Adeline Barthelemy, Stoyan Ivanov, Maya Hassane, Josette Fontaine, Béatrice Heurtault, Benoit Frisch, Christelle Faveeuw, Christophe Paget, François Trottein
: Influenza A virus infection can predispose to potentially devastating secondary bacterial infections. Invariant natural killer T (iNKT) cells are unconventional, lipid-reactive T lymphocytes that exert potent immunostimulatory functions. Using a mouse model of postinfluenza invasive secondary pneumococcal infection, we sought to establish whether α-galactosylceramide (α-GalCer [a potent iNKT cell agonist that is currently in clinical development]) could limit bacterial superinfection...
November 1, 2016: MBio
https://www.readbyqxmd.com/read/27797959/hookworm-recombinant-protein-promotes-regulatory-t-cell-responses-that-suppress-experimental-asthma
#15
Severine Navarro, Darren A Pickering, Ivana B Ferreira, Linda Jones, Stephanie Ryan, Sally Troy, Andrew Leech, Peter J Hotez, Bin Zhan, Thewarach Laha, Roger Prentice, Tim Sparwasser, John Croese, Christian R Engwerda, John W Upham, Valerie Julia, Paul R Giacomin, Alex Loukas
In the developed world, declining prevalence of some parasitic infections correlates with increased incidence of allergic and autoimmune disorders. Moreover, experimental human infection with some parasitic worms confers protection against inflammatory diseases in phase 2 clinical trials. Parasitic worms manipulate the immune system by secreting immunoregulatory molecules that offer promise as a novel therapeutic modality for inflammatory diseases. We identify a protein secreted by hookworms, anti-inflammatory protein-2 (AIP-2), that suppressed airway inflammation in a mouse model of asthma, reduced expression of costimulatory markers on human dendritic cells (DCs), and suppressed proliferation ex vivo of T cells from human subjects with house dust mite allergy...
October 26, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27796442/congenic-mapping-identifies-a-novel-idd9-subregion-regulating-type-1-diabetes-in-nod-mice
#16
Bixuan Lin, Ashley E Ciecko, Erin MacKinney, David V Serreze, Yi-Guang Chen
Type 1 diabetes (T1D) results from complex interactions between genetic and environmental factors. The nonobese diabetic (NOD) mouse develops spontaneous T1D and has been used extensively to study the genetic control of this disease. T1D is suppressed in NOD mice congenic for the C57BL/10 (B10)-derived Idd9 resistance region on chromosome 4. Previous studies conducted by other investigators have identified four subregions (Idd9.1, Idd9.2, Idd9.3, and Idd9.4) where B10-derived genes suppress T1D development in NOD mice...
October 28, 2016: Immunogenetics
https://www.readbyqxmd.com/read/27791087/human-v%C3%AE-2-t-cells-are-a-major-source-of-interleukin-9
#17
Christian Peters, Robert Häsler, Daniela Wesch, Dieter Kabelitz
Vδ2Vγ9 T cells are the dominant γδ T-cell subset in human peripheral blood. Vδ2 T cells recognize pyrophosphate molecules derived from microbes or tumor cells; hence, they play a role in antimicrobial and antitumor immunity. TGF-β, together with IL-15, induces a regulatory phenotype in Vδ2 T cells, characterized by forkhead box protein P3 (FoxP3) expression and suppressive activity on CD4 T-cell activation. We performed a genome-wide transcriptome analysis and found that the same conditions (TGF-β plus IL-15) strongly enhanced the expression of additional genes in Vδ2 T cells, including IKAROS family zinc finger 4 (IKZF4; Eos), integrin subunit alpha E (ITGAE; CD103/αEβ7), and IL9 This up-regulation was associated with potent IL-9 production as revealed by flow cytometry and multiplex analysis of cell culture supernatants...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27783947/inflammatory-th1-and-th17-in-the-intestine-are-each-driven-by-functionally-specialized-dendritic-cells-with-distinct-requirements-for-myd88
#18
Jie Liang, Hsin-I Huang, Fernanda P Benzatti, Amelia B Karlsson, Junyi J Zhang, Nourhan Youssef, Averil Ma, Laura P Hale, Gianna E Hammer
Normal dynamics between microbiota and dendritic cells (DCs) support modest numbers of T cells, yet these do not cause inflammation. The DCs that induce inflammatory T cells and the signals that drive this process remain unclear. Here, we demonstrate that small intestine DCs lacking the signaling attenuator A20 induce inflammatory T cells and that the signals perceived and antigen-presenting cell (APC) functions are unique for different DC subsets. Thus, although CD103(+)CD11b(-) DCs exclusively instruct IFNγ(+) T cells, CD103(+)CD11b(+) DCs exclusively instruct IL-17(+) T cells...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27783386/characterization-of-resident-lymphocytes-in-human-pancreatic-islets
#19
Miljana Radenkovic, Kristina Uvebrant, Oskar Skog, Luis Sarmiento, Jeanette Avartsson, Peter Storm, Petter Vickman, Per-Anders Bertilsson, Malin Fex, Olle Korsgren, Corrado M Cilio
The current view of type 1 diabetes (T1D) is that it is an immune-mediated disease where lymphocytes infiltrate the pancreatic islets, promote killing of beta cells and cause overt diabetes. Although tissue resident immune cells have been demonstrated in several organs, the composition of lymphocytes in human healthy pancreatic islets have been scarcely studied. Here we aimed to investigate the phenotype of immune cells associated to human islets of non-diabetic organ donors. A flow cytometry analysis of isolated islets from perfused pancreases (n=38) was employed to identify alpha, beta, T, NK and B cells...
October 26, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27776108/programs-for-the-persistence-vigilance-and-control-of-human-cd8-lung-resident-memory-t-cells
#20
Pleun Hombrink, Christina Helbig, Ronald A Backer, Berber Piet, Anna E Oja, Regina Stark, Giso Brasser, Aldo Jongejan, René E Jonkers, Benjamin Nota, Onur Basak, Hans C Clevers, Perry D Moerland, Derk Amsen, René A W van Lier
Tissue-resident memory T cells (TRM cells) in the airways mediate protection against respiratory infection. We characterized TRM cells expressing integrin αE (CD103) that reside within the epithelial barrier of human lungs. These cells had specialized profiles of chemokine receptors and adhesion molecules, consistent with their unique localization. Lung TRM cells were poised for rapid responsiveness by constitutive expression of deployment-ready mRNA encoding effector molecules, but they also expressed many inhibitory regulators, suggestive of programmed restraint...
December 2016: Nature Immunology
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