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https://www.readbyqxmd.com/read/28231307/differential-regulation-of-c5a-receptor-1-in-innate-immune-cells-during-the-allergic-asthma-effector-phase
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28109087/cd103-cell-growth-factor-flt3l-enhances-the-efficacy-of-immune-checkpoint-blockades-in-murine-glioblastoma-model
#10
Xiaolin Miao, Yiqi Chen, Ke Hao, Meiqin Zheng, Bingyu Chen, Kaiqiang Li, Ying Wang, Wei Zhang, Yu Zhang, Xiaozhou Mou, Shanshan Jiang, Zhen Wang
Glioblastoma is a lethal disease featured with a high proliferation of tumor cells, excessive angiogenesis, and heavydrug resistance. The overall survival of glioblastoma patients was dismal even with intensive standard care. Recent advantages in immune checkpoint blockades are changing the treatment of cancers. However, the efficacy of immune checkpoint blockades in glioblastoma were unclear. Here, we investigated the roles of CD103<sup>+</sup> cells in regulating the effects of immune checkpoint blockades in glioblastoma mouse models...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28108233/murine-cd103-dendritic-cells-protect-against-steatosis-progression-towards-steatohepatitis
#11
Eva-Carina Heier, Anna Meier, Henrike Julich-Haertel, Sonja Djudjaj, Monica Rau, Thomas Tschernig, Andreas Geier, Peter Boor, Frank Lammert, Veronika Lukacs-Kornek
BACKGROUND: Non-alcoholic fatty liver (NAFL) is the hepatic consequence of metabolic syndrome and can progress to non-alcoholic steatohepatitis (NASH). The identification of molecular and cellular factors that determine the progression of NASH and lead to irreversible hepatocellular damage are crucial. Dendritic cells (DCs) represent a heterogeneous cell population among which CD103(+) DCs play a significant role in immunity and tolerance. METHODS: Steatosis progression towards steatohepatitis was analyzed using multicolor FACS analyses, cytokine and qPCR array in high sucrose diet (HSD) and methionine and choline deficient diet (MCD) fed wild-type and Batf3 (Basic Leucine Zipper Transcription Factor, ATF-Like-3) deficient animals, which lack CD103(+) DCs (classical type-1 DC, cDC1s)...
January 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28099920/prognostic-implications-of-intratumoral-cd103-tumor-infiltrating-lymphocytes-in-pulmonary-squamous-cell-carcinoma
#12
Jaemoon Koh, Sehui Kim, Moon-Young Kim, Heounjeong Go, Yoon Kyung Jeon, Doo Hyun Chung
CD103 is the αE subunit of αEβ7 integrin that is expressed in tissue-resident memory T cells, where it promotes cytotoxic T cell responses against tumors. However, little is known about its expression or clinicopathological implications in non-small cell lung cancer (NSCLC). This study investigated the prognostic implications of CD103+ tumor-infiltrating lymphocytes (TILs) in NSCLC. We established two cohorts: patients with resected NSCLC (n = 132) and patients with pulmonary squamous cell carcinoma (pSCC), a subset of NSCLC (n = 378), to estimate the prognostic significance of CD103+ TILs...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28087652/differential-regulation-of-cd103-%C3%AE-e-integrin-expression-in-human-dendritic-cells-by-retinoic-acid-and-toll-like-receptor-ligands
#13
Mandi M Roe, Steve Swain, T Andrew Sebrell, Marisa A Sewell, Madison M Collins, Brian A Perrino, Phillip D Smith, Lesley E Smythies, Diane Bimczok
CD103 (αE integrin) is an important dendritic cell (DC) marker that characterizes functionally distinct DC subsets in mice and humans. However, the mechanism by which CD103 expression is regulated in human DCs and the role of CD103 for DC function are not very well understood. Here, we show that retinoic acid (RA) treatment of human monocyte-derived DCs (MoDCs) increased the ability of the DCs to synthesize RA and induced MoDC expression of CD103 and β7 at the mRNA and protein level. In contrast, RA was unable to induce the expression of CD103 in primary human DCs isolated from the gastric mucosa...
January 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28081153/dermal-%C3%AE-%C3%AE-t-cells-do-not-freely-re-circulate-out-of-skin-and-produce-il-17-to-promote-neutrophil-infiltration-during-primary-contact-hypersensitivity
#14
Xiaodong Jiang, Chang Ook Park, Jenna Geddes Sweeney, Min Jae Yoo, Olivier Gaide, Thomas Seth Kupper
The role of mouse dermal γδ T cells in inflammatory skin disorders and host defense has been studied extensively. It is known that dendritic epidermal T cells (DETC) have a monomorphic γδ T cell receptor (TCR) and reside in murine epidermis from birth. We asked if dermal γδ cells freely re-circulated out of skin, or behaved more like dermal resident memory T cells (TRM) in mice. We found that, unlike epidermal γδ T cells (DETC), dermal γδ cells are not homogeneous with regard to TCR, express the tissue resident T cell markers CD69 and CD103, bear skin homing receptors, and produce IL-17 and IL-22...
2017: PloS One
https://www.readbyqxmd.com/read/28061951/role-and-contribution-of-pulmonary-cd103-dendritic-cells-in-the-adaptive-immune-response-to-mycobacterium-tuberculosis
#15
Vanessa Hui Qi Koh, See Liang Ng, Michelle Lay Teng Ang, Wenwei Lin, Christiane Ruedl, Sylvie Alonso
Despite international control programmes, the global burden of tuberculosis remains enormous. Efforts to discover novel drugs have largely focused on targeting the bacterium directly. Alternatively, manipulating the host immune response may represent a valuable approach to enhance immunological clearance of the bacilli, but necessitates a deeper understanding of the immune mechanisms associated with protection against Mycobacterium tuberculosis infection. Here, we examined the various dendritic cells (DC) subsets present in the lung and draining lymph nodes (LN) from mice intra-tracheally infected with M...
January 2017: Tuberculosis
https://www.readbyqxmd.com/read/28051085/intrinsic-4-1bb-signals-are-indispensable-for-the-establishment-of-an-influenza-specific-tissue-resident-memory-cd8-t-cell-population-in-the-lung
#16
A C Zhou, L E Wagar, M E Wortzman, T H Watts
The induction of long-lived heterotypic T-cell protection against influenza virus remains elusive, despite the conservation of T-cell epitopes. T-cell protection against influenza is critically dependent on lung-resident memory T cells (Trm). Here we show that intranasal administration of 4-1BBL along with influenza nucleoprotein in a replication-defective adenovirus vector to influenza pre-immune mice induces a remarkably stable circulating effector memory CD8 T-cell population characterized by higher IL-7Rα expression than control-boosted T cells, as well as a substantial lung parenchymal CD69(+) CD8 Trm population, including both CD103(+) and CD103(-) cells...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28051084/enrichment-of-herpes-simplex-virus-type-2-hsv-2-reactive-mucosal-t-cells-in-the-human-female-genital-tract
#17
C M Posavad, L Zhao, L Dong, L Jin, C E Stevens, A S Magaret, C Johnston, A Wald, J Zhu, L Corey, D M Koelle
Local mucosal cellular immunity is critical in providing protection from HSV-2. To characterize and quantify HSV-2-reactive mucosal T cells, lymphocytes were isolated from endocervical cytobrush and biopsy specimens from 17 HSV-2-infected women and examined ex vivo for the expression of markers associated with maturation and tissue residency and for functional T-cell responses to HSV-2. Compared with their circulating counterparts, cervix-derived CD4+ and CD8+ T cells were predominantly effector memory T cells (CCR7-/CD45RA-) and the majority expressed CD69, a marker of tissue residency...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28024958/outer-membrane-vesicles-harboring-modified-lipid-a-moiety-augment-the-efficacy-of-an-influenza-vaccine-exhibiting-reduced-endotoxicity-in-a-mouse-model
#18
Tae-Young Lee, Chang-Ung Kim, Eun-Hye Bae, Sang-Hwan Seo, Dae Gwin Jeong, Sun-Woo Yoon, Kyu-Tae Chang, Young Sang Kim, Sang-Hyun Kim, Doo-Jin Kim
Influenza is an acute respiratory disease and a major health problem worldwide. Since mucosal immunity plays a critical role in protection against influenza virus infection, mucosal immunization is considered a promising vaccination route. However, except for live-attenuated vaccines, there are no effective killed or recombinant mucosal influenza vaccines to date. Outer membrane vesicles (OMVs) are nano-sized vesicles produced by gram-negative bacteria, and contain various bacterial components capable of stimulating the immune system of the host...
December 23, 2016: Vaccine
https://www.readbyqxmd.com/read/28018343/very-late-antigen-1-marks-functional-tumor-resident-cd8-t-cells-and-correlates-with-survival-of-melanoma-patients
#19
Timothy Murray, Silvia A Fuertes Marraco, Petra Baumgaertner, Natacha Bordry, Laurène Cagnon, Alena Donda, Pedro Romero, Grégory Verdeil, Daniel E Speiser
A major limiting factor in the success of immunotherapy is tumor infiltration by CD8(+) T cells, a process that remains poorly understood. In the present study, we characterized homing receptors expressed by human melanoma-specific CD8(+) T cells. Our data reveal that P-selectin binding and expression of the retention integrin, very late antigen (VLA)-1, by vaccine-induced T cells correlate with longer patient survival. Furthermore, we demonstrate that CD8(+)VLA-1(+) tumor-infiltrating lymphocytes (TILs) are highly enriched in melanoma metastases in diverse tissues...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28004802/targeting-dendritic-cells-to-accelerate-t-cell-activation-overcomes-a-bottleneck-in-tuberculosis-vaccine-efficacy
#20
Kristin L Griffiths, Mushtaq Ahmed, Shibali Das, Radha Gopal, William Horne, Terry D Connell, Kelly D Moynihan, Jay K Kolls, Darrell J Irvine, Maxim N Artyomov, Javier Rangel-Moreno, Shabaana A Khader
The development of a tuberculosis (TB) vaccine that induces sterilizing immunity to Mycobacterium tuberculosis infection has been elusive. Absence of sterilizing immunity induced by TB vaccines may be due to delayed activation of mucosal dendritic cells (DCs), and subsequent delay in antigen presentation and activation of vaccine-induced CD4(+) T-cell responses. Here we show that pulmonary delivery of activated M. tuberculosis antigen-primed DCs into vaccinated mice, at the time of M. tuberculosis exposure, can overcome the delay in accumulation of vaccine-induced CD4(+) T-cell responses...
December 22, 2016: Nature Communications
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