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Journal of Immunology: Official Journal of the American Association of Immunologists

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https://read.qxmd.com/read/30760623/increased-gitrl-impairs-the-function-of-myeloid-derived-suppressor-cells-and-exacerbates-primary-sj%C3%A3-gren-syndrome
#1
Jie Tian, Ke Rui, Yue Hong, Xiaohui Wang, Fan Xiao, Xiang Lin, Jie Ma, Hongye Guo, Huaxi Xu, Kongyang Ma, Dong Xu, Dongzhou Liu, Yan Zhao, Liwei Lu, Shengjun Wang
Although the expansion of myeloid-derived suppressor cells (MDSCs) has been reported in autoimmune disorders, it is largely unclear how MDSCs contribute to the development of primary Sjögren syndrome (pSS). In this study, we found significantly increased MDSCs with gradually diminished suppressive capacity during disease development in mice with experimental Sjögren syndrome (ESS). The ligand for glucocorticoid-induced TNFR family-related protein (GITRL) was increased along ESS progression, whereas the increased GITRL was found to attenuate the immunosuppressive function of MDSCs...
February 13, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30760622/a20-orchestrates-inflammatory-response-in-the-oral-mucosa-through-restraining-nf-%C3%AE%C2%BAb-activity
#2
Yajie Li, Erin C Mooney, Sara E Holden, Xia-Juan Xia, David J Cohen, Scott W Walsh, Averil Ma, Sinem E Sahingur
Deregulated immune response to a dysbiotic resident microflora within the oral cavity leads to chronic periodontal disease, local tissue destruction, and various systemic complications. To preserve tissue homeostasis, inflammatory signaling pathways involved in the progression of periodontitis must be tightly regulated. A20 (TNFAIP3), a ubiquitin-editing enzyme, has emerged as one of the key regulators of inflammation. Yet, the function of A20 in the oral mucosa and the biological pathways in which A20 mitigates periodontal inflammation remain elusive...
February 13, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30760621/flexamers-a-double-tag-for-universal-generation-of-versatile-peptide-mhc-multimers
#3
Manuel Effenberger, Andreas Stengl, Kilian Schober, Maria Gerget, Maximilian Kampick, Thomas R Müller, Dominik Schumacher, Jonas Helma, Heinrich Leonhardt, Dirk H Busch
Peptide-MHC (pMHC) multimers have become a valuable tool for immunological research, clinical immune monitoring, and immunotherapeutic applications. Biotinylated tetramers, reversible Streptamers, or dye-conjugated pMHC multimers are distinct pMHC reagents tailored for T cell identification, traceless T cell isolation, or TCR characterization, respectively. The specific applicability of each pMHC-based reagent is made possible either through conjugation of probes or reversible multimerization in separate production processes, which is laborious, time-consuming, and prone to variability between the different types of pMHC reagents...
February 13, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30760620/differential-influence-of-il-9-and-il-17-on-actin-cytoskeleton-regulates-the-migration-potential-of-human-keratinocytes
#4
Sreya Das, Srisathya Srinivasan, Ankita Srivastava, Sushant Kumar, Gargi Das, Suman Das, Alka Dwivedi, Atharva Karulkar, Khushi Makkad, Richa Bilala, Ankit Gupta, Abhijeet Sawant, Chitra Nayak, Prakriti Tayalia, Rahul Purwar
T cells mediate skin immune surveillance by secreting specific cytokines and regulate numerous functions of keratinocytes, including migration during homeostasis and disease pathogenesis. Keratinocyte migration is mediated mainly by proteolytic cleavage of the extracellular matrix and/or by cytoskeleton reorganization. However, the cross-talk between T cell cytokines and actomyosin machinery of human primary keratinocytes (HPKs), which is required for cytoskeleton reorganization and subsequent migration, remains poorly examined...
February 13, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30760619/human-blood-and-tonsil-plasmacytoid-dendritic-cells-display-similar-gene-expression-profiles-but-exhibit-differential-type-i-ifn-responses-to-influenza-a-virus-infection
#5
Sindhu Vangeti, Jens Gertow, Meng Yu, Sang Liu, Faezzah Baharom, Saskia Scholz, Danielle Friberg, Magnus Starkhammar, Alexander Ahlberg, Anna Smed-Sörensen
Influenza A virus (IAV) infection constitutes an annual health burden across the globe. Plasmacytoid dendritic cells (PDCs) are central in antiviral defense because of their superior capacity to produce type I IFNs in response to viruses. Dendritic cells (DCs) differ depending on their anatomical location. However, only limited host-pathogen data are available from the initial site of infection in humans. In this study, we investigated how human tonsil PDCs, likely exposed to virus because of their location, responded to IAV infection compared with peripheral blood PDCs...
February 13, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30760618/oral-treatment-with-bt-11-ameliorates-inflammatory-bowel-disease-by-enhancing-regulatory-t-cell-responses-in-the-gut
#6
Andrew Leber, Raquel Hontecillas, Victoria Zoccoli-Rodriguez, Jyoti Chauhan, Josep Bassaganya-Riera
Inflammatory bowel disease (IBD) is an expanding autoimmune disease afflicting millions that remains difficult to treat due to the accumulation of multiple immunological changes. BT-11 is an investigational new drug for IBD that is orally active, gut restricted, and targets the lanthionine synthetase C-like 2 immunometabolic pathway. CD25+ FOXP3+ CD4+ T cells are increased locally within the colon of BT-11-treated mice in Citrobacter rodentium and IL-10-/- mouse models of colitis. The maintained efficacy of BT-11 in the absence of IL-10 combined with the loss of efficacy when direct cell-cell interactions are prevented suggest that the regulatory T cell (Treg)-related elements of suppression are cell contact-mediated...
February 13, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30745463/upper-airway-cell-transcriptomics-identify-a-major-new-immunological-phenotype-with-strong-clinical-correlates-in-young-children-with-acute-wheezing
#7
Siew-Kim Khoo, James Read, Kimberley Franks, Guicheng Zhang, Joelene Bizzintino, Laura Coleman, Christopher McCrae, Lisa Öberg, Niamh M Troy, Franciska Prastanti, Janet Everard, Stephen Oo, Meredith L Borland, Rose A Maciewicz, Peter N Le Souëf, Ingrid A Laing, Anthony Bosco
Asthma exacerbations are triggered by rhinovirus infections. We employed a systems biology approach to delineate upper-airway gene network patterns underlying asthma exacerbation phenotypes in children. Cluster analysis unveiled distinct IRF7hi versus IRF7lo molecular phenotypes, the former exhibiting robust upregulation of Th1/type I IFN responses and the latter an alternative signature marked by upregulation of cytokine and growth factor signaling and downregulation of IFN-γ. The two phenotypes also produced distinct clinical phenotypes...
February 11, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30745462/hypersensitive-ifn-responses-in-lupus-keratinocytes-reveal-key-mechanistic-determinants-in-cutaneous-lupus
#8
Lam C Tsoi, Grace A Hile, Celine C Berthier, Mrinal K Sarkar, Tamra J Reed, Jianhua Liu, Ranjitha Uppala, Matthew Patrick, Kalpana Raja, Xianying Xing, Enze Xing, Kevin He, Johann E Gudjonsson, J Michelle Kahlenberg
Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which 70% of patients experience disfiguring skin inflammation (grouped under the rubric of cutaneous lupus erythematosus [CLE]). There are limited treatment options for SLE and no Food and Drug Administration-approved therapies for CLE. Studies have revealed that IFNs are important mediators for SLE and CLE, but the mechanisms by which IFNs lead to disease are still poorly understood. We aimed to investigate how IFN responses in SLE keratinocytes contribute to development of CLE...
February 11, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30745461/combined-blockade-of-tnf-%C3%AE-and-il-17a-alleviates-progression-of-collagen-induced-arthritis-without-causing-serious-infections-in-mice
#9
Fang Shen, Akash H Verma, Amy Volk, Brian Jones, Bianca M Coleman, Matthew J Loza, Ravi Malaviya, Beverley Moore, Daniel Weinstock, M Merle Elloso, Sarah L Gaffen, Tatiana Ort
The cytokines TNF-α and IL-17A are elevated in a variety of autoimmune diseases, including rheumatoid arthritis. Both cytokines are targets of several biologic drugs used in the clinic, but unfortunately many patients are refractory to these therapies. IL-17A and TNF-α are known to mediate signaling synergistically to drive expression of inflammatory genes. Hence, combined blockade of TNF-α and IL-17A represents an attractive treatment strategy in autoimmune settings where monotherapy is not fully effective...
February 11, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30745460/glatiramer-acetate-stimulates-regulatory-b-cell-functions
#10
Kahina Amrouche, Jacques-Olivier Pers, Christophe Jamin
The control of the activities of regulatory B (Breg) cells in immune disorders is an emerging therapeutic strategy for the recovery of immune homeostasis. Manipulating B cells using numerous drugs in vivo affect their regulatory functions, although a direct link has not yet been demonstrated. Glatiramer acetate (GA) is a synthetic polypeptide that is used in the treatment of inflammatory and autoimmune diseases. We experimented on an in vitro coculture system to determine its direct effects on the Breg cell properties of human B cells...
February 11, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30745459/self-versus-nonself-discrimination-by-the-soluble-complement-regulators-factor-h-and-fhl-1
#11
Arthur Dopler, Leonie Guntau, Markus J Harder, Annette Palmer, Britta Höchsmann, Hubert Schrezenmeier, Thomas Simmet, Markus Huber-Lang, Christoph Q Schmidt
The plasma proteins Factor H (FH) and its alternate splice variant FH-like protein 1 (FHL-1) are the major regulators of the complement alternative pathway. The indiscriminate nature of alternative pathway activation necessitates the regulators to be host selective, but the underlying principles of selectivity remained largely elusive. By analyzing human FH and FHL-1 for protection of different host and foreign cells (rabbit and yeast), we uncovered a 2-fold discriminatory mechanism of FH in favor of self: relative to FHL-1, FH exhibits a regulatory benefit on self but importantly, also, a regulatory penalty on nonself surfaces, yielding a selectivity factor of ∼2...
February 11, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30745458/monocytes-represent-one-source-of-bacterial-shielding-from-antibiotics-following-influenza-virus-infection
#12
Karl J Fischer, Vijaya Kumar Yajjala, Shruti Bansal, Christopher Bauer, Ruiling Chen, Keer Sun
Methicillin-resistant Staphylococcus aureus has emerged as a significant contributor to morbidity and mortality associated with influenza infection. In this study, we show in a mouse model that preceding influenza infection promotes S. aureus resistance to killing by antibiotics. This resistance coincides with influenza-induced accumulation of inflammatory monocytes in the lung. CCR type 2 (CCR2) is responsible for pulmonary monocyte recruitment after influenza infection. We found that antibiotic-treated Ccr2-deficient (Ccr2-/- ) mice exhibit significantly improved bacterial control and survival from influenza and methicillin-resistant S...
February 11, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30737275/programming-effects-of-pubertal-lipopolysaccharide-treatment-in-male-and-female-cd-1-mice
#13
Rupali Sharma, Spencer van Mil, Brett Melanson, Bronwen J Thomas, Jasmine Rooke, Jean-François Mallet, Chantal Matar, Jaclyn M Schwarz, Nafissa Ismail
Puberty is a critical period of development marked by sexual, immune, and neural maturation. Exposure to stress during this period can lead to enduring changes in brain functioning and in behavior; however, the underlying mechanisms and the programming effects of stress during puberty remain unknown. Therefore, the objective of this study was to investigate the programming effects of pubertal immune challenge in response to a homotypic stressor later in life in CD-1 mice. Age and sex differences in the peripheral and central cytokine levels, along with sickness behavior and telemetry data, were analyzed following the secondary treatment...
February 8, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30737274/elevated-expression-of-macrophage-migration-inhibitory-factor-promotes-inflammatory-bone-resorption-induced-in-a-mouse-model-of-periradicular-periodontitis
#14
Mohammed Howait, Abdullah Albassam, Chiaki Yamada, Hajime Sasaki, Laila Bahammam, Mariane Maffei Azuma, Luciano Tavares Angelo Cintra, Abhay R Satoskar, Satoru Yamada, Robert White, Toshihisa Kawai, Alexandru Movila
Locally produced osteoclastogenic factor RANKL plays a critical role in the development of bone resorption in periradicular periodontitis. However, because RANKL is also required for healthy bone remodeling, it is plausible that a costimulatory molecule that upregulates RANKL production in inflammatory periradicular periodontitis may be involved in the pathogenic bone loss processes. We hypothesized that macrophage migration inhibitory factor (MIF) would play a role in upregulating the RANKL-mediated osteoclastogenesis in the periradicular lesion...
February 8, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30737273/new-insights-into-lymphocyte-differentiation-and-aging-from-telomere-length-and-telomerase-activity-measurements
#15
Tinhinane Fali, Laura Papagno, Charles Bayard, Yanis Mouloud, Jacques Boddaert, Delphine Sauce, Victor Appay
αβ CD8+ , γδ, and NK lymphocytes are fundamental effector cells against viruses and tumors. These cells can be divided into multiple subsets according to their phenotype. Based on progressive telomere attrition from naive to late effector memory cells, human CD8+ T cell subsets have been positioned along a pathway of differentiation, which is also considered as a process of lymphocyte aging or senescence. A similar categorization has not been clearly established for γδ and NK cell populations. Moreover, the distinction between the aging of these populations due to cellular differentiation or due to the chronological age of the donor has not been formally considered...
February 8, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30737272/short-chain-fatty-acids-from-cutibacterium-acnes-activate-both-a-canonical-and-epigenetic-inflammatory-response-in-human-sebocytes
#16
James A Sanford, Alan M O'Neill, Christos C Zouboulis, Richard L Gallo
The regulation of cutaneous inflammatory processes is essential for the human skin to maintain homeostasis in the presence of the dense communities of resident microbes that normally populate this organ. Forming the hair follicle-associated sebaceous gland, sebocytes are specialized lipid-producing cells that can release inflammatory mediators. Cytokine and chemokine expression by pilosebaceous epithelial cells (i.e., sebocytes and follicular keratinocytes) has been proposed to contribute to the common human skin disease acne vulgaris...
February 8, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30728214/correction-a-novel-neutralizing-antibody-specific-to-the-de-loop-of-vp1-can-inhibit-ev-d68-infection-in-mice
#17
Huiwen Zheng, Jingjing Wang, Bingxiang Li, Lei Guo, Heng Li, Jie Song, Zening Yang, Hongzhe Li, Haitao Fan, Xing Huang, Haiting Long, Chen Cheng, Manman Chu, Zhanlong He, Wenhai Yu, Jiaqi Li, You Gao, Ruotong Ning, Nan Li, Jinxi Yang, Qiongwen Wu, Haijing Shi, Ming Sun, Longding Liu
No abstract text is available yet for this article.
February 6, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30728213/tonic-signaling-and-its-effects-on-lymphopoiesis-of-car-armed-hematopoietic-stem-and-progenitor-cells
#18
Susann Albert, Stefanie Koristka, Alexander Gerbaulet, Marc Cartellieri, Claudia Arndt, Anja Feldmann, Nicole Berndt, Liliana R Loureiro, Malte von Bonin, Gerhard Ehninger, Anne Eugster, Ezio Bonifacio, Martin Bornhäuser, Michael P Bachmann, Armin Ehninger
Long-term survival of adoptively transferred chimeric Ag receptor (CAR) T cells is often limited. Transplantation of hematopoietic stem cells (HSCs) transduced to express CARs could help to overcome this problem as CAR-armed HSCs can continuously deliver CAR+ multicell lineages (e.g., T cells, NK cells). In dependence on the CAR construct, a variable extent of tonic signaling in CAR T cells was reported; thus, effects of CAR-mediated tonic signaling on the hematopoiesis of CAR-armed HSCs is unclear. To assess the effects of tonic signaling, two CAR constructs were established and analyzed 1) a signaling CAR inducing a solid Ag-independent tonic signaling termed CAR-28/ζ and 2) a nonstimulating control CAR construct lacking intracellular signaling domains termed CAR-Stop...
February 6, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30728212/cutting-edge-core-binding-factor-%C3%AE-is-required-for-group-2-innate-lymphoid-cell-activation
#19
Xiaofei Shen, Mingwei Liang, Xiangyu Chen, Muhammad Asghar Pasha, Shanti S D'Souza, Kelsi Hidde, Jennifer Howard, Dil Afroz Sultana, Ivan Ting Hin Fung, Longyun Ye, Jiexue Pan, Gang Liu, James R Drake, Lisa A Drake, Jinfang Zhu, Avinash Bhandoola, Qi Yang
Group 2 innate lymphoid cells (ILC2) are tissue-resident, long-lived innate effector cells implicated in allergy and asthma. Upon activation, mature ILC2 rapidly secrete large amounts of type-2 cytokines and other effector molecules. The molecular pathways that drive ILC2 activation are not well understood. In this study, we report that the transcriptional controller core binding factor β (CBFβ) is required for ILC2 activation. Deletion or inhibition of CBFβ did not impair the maintenance of ILC2 at homeostasis but abolished ILC2 activation during allergic airway inflammation...
February 6, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30728211/correction-high-resolution-genetic-and-phenotypic-analysis-of-kir2dl1-alleles-and-their-association-with-pre-eclampsia
#20
Oisín Huhn, Olympe Chazara, Martin A Ivarsson, Christelle Retière, Timothy C Venkatesan, Paul J Norman, Hugo G Hilton, Jyothi Jayaraman, James A Traherne, John Trowsdale, Mitsutero Ito, Christiane Kling, Peter Parham, Hormas Ghadially, Ashley Moffett, Andrew M Sharkey, Francesco Colucci
No abstract text is available yet for this article.
February 6, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
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