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IL-10 as a Th2 Cytokine: Differences Between Mice and Humans.

Mahima T Rasquinha, Meghna Sur, Ninaad Lasrado, Jay Reddy,

The discovery of IL-10 more than 30 years ago marked the beginning of our understanding of how cytokines regulate immune responses, based on cross-regulation between Th1 and Th2 cytokines. Although multiple cell types were shown to produce IL-10, its identity as a Th2 cytokine remained strong because it was rigidly ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, 207(9):2205-2215]

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More Than Two to Tango: Mesenchymal Cells Are Required for Early T Cell Development.

Michele K Anderson,

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, 207(9):2203-2204]

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SysInflam HuDB, a Web Resource for Mining Human Blood Cells Transcriptomic Data Associated with Systemic Inflammatory Responses to Sepsis.

Mohammed Toufiq, Susie Shih Yin Huang, Sabri Boughorbel, Mohamed Alfaki, Darawan Rinchai, Luis R Saraiva, Damien Chaussabel, Mathieu Garand,

Sepsis develops after a dysregulated host inflammatory response to a systemic infection. Identification of sepsis biomarkers has been challenging because of the multifactorial causes of disease susceptibility and progression. Public transcriptomic data are a valuable resource for mechanistic discoveries and cross-studies concordance of heterogeneous diseases. Nonetheless, the approach requires structured ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, 207(9):2195-2202]

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J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, 207(9):2193]

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Maternal Monocytes Respond to Cell-Free Fetal DNA and Initiate Key Processes of Human Parturition.

Nazanin Yeganeh Kazemi, Bohdana Fedyshyn, Shari Sutor, Yaroslav Fedyshyn, Svetomir Markovic, Elizabeth Ann L Enninga,

Throughout gestation, the maternal immune system is tightly modulated to allow growth of a semiallogeneic fetus. During the third trimester, the maternal immune system shifts to a proinflammatory phenotype in preparation for labor. What induces this shift remains unclear. Cell-free fetal DNA (cffDNA) is shed by the placenta and enters ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
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IL-15 Trans-Presentation Is an Autonomous, Antigen-Independent Process.

Ádám Kenesei, Julianna Volkó, Nikoletta Szalóki, Gábor Mocsár, Károly Jambrovics, Zoltán Balajthy, Andrea Bodnár, Katalin Tóth, Thomas A Waldmann, György Vámosi,

IL-15 plays a pivotal role in the long-term survival of T cells and immunological memory. Its receptor consists of three subunits (IL-15Rα, IL-2/15Rβ, and γ<sub>c</sub>). IL-15 functions mainly via <i>trans</i>-presentation (TP), during which an APC expressing IL-15 bound to IL-15Rα presents the ligand to the βγ<sub>c</sub> receptor-heterodimer on a neighboring ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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Cutting Edge: DOCK8 Regulates a Subset of Dendritic Cells That Is Critical for the Development of Experimental Autoimmune Encephalomyelitis.

Asanga Weliwitigoda, Pushpalatha Palle, Melissa Gessner, Nicholas W Hubbard, Mohamed Oukka, Estelle Bettelli,

Dedicator of cytokinesis 8 (DOCK8) is a guanine nucleotide exchange factor with an essential role in cytoskeletal rearrangement, cell migration, and survival of various immune cells. Interestingly, DOCK8-deficient mice are resistant to the development of experimental autoimmune encephalomyelitis (EAE). To understand if EAE resistance in these mice results from an ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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Cutting Edge: Caspase-8 Is a Linchpin in Caspase-3 and Gasdermin D Activation to Control Cell Death, Cytokine Release, and Host Defense during Influenza A Virus Infection.

Yaqiu Wang, Rajendra Karki, Min Zheng, Balabhaskararao Kancharana, SangJoon Lee, Sannula Kesavardhana, Baranda S Hansen, Shondra M Pruett-Miller, Thirumala-Devi Kanneganti,

Programmed cell death (PCD) is essential for the innate immune response, which serves as the first line of defense against pathogens. Caspases regulate PCD, immune responses, and homeostasis. Caspase-8 specifically plays multifaceted roles in PCD pathways including pyroptosis, apoptosis, and necroptosis. However, because caspase-8-deficient mice are embryonically lethal, little is ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
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Maternal and Infant Immune Repertoire Sequencing Analysis Identifies Distinct Ig and TCR Development in Term and Preterm Infants.

Brian L Le, Renan Sper, Sandra C A Nielsen, Silvia Pineda, Quoc-Hung Nguyen, Ji-Yeun Lee, Scott D Boyd, Tippi C MacKenzie, Marina Sirota,

Preterm labor (PTL) is the leading cause of neonatal morbidity and mortality worldwide. Whereas many studies have investigated the maternal immune responses that cause PTL, fetal immune cell activation has recently been raised as an important contributor to the pathogenesis of PTL. In this study, we analyzed lymphocyte receptor repertoires ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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STAT3 Gain-of-Function Mutations Underlie Deficiency in Human Nonclassical CD16+ Monocytes and CD141+ Dendritic Cells.

Daniel Korenfeld, Kate Roussak, Sabrina Dinkel, Tiphanie P Vogel, Henry Pollack, Joseph Levy, Jennifer W Leiding, Joshua Milner, Megan Cooper, Eynav Klechevsky,

Genetic analysis of human inborn errors of immunity has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. The STAT family of transcription factors orchestrate hematopoietic cell differentiation. Patients with de novo activating mutations of <i>STAT3</i> present with multiorgan autoimmunity, lymphoproliferation, and recurrent ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
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Development of Neutralizing Multimeric Nanobody Constructs Directed against IL-13: From Immunization to Lead Optimization.

Philippe J-L Y Gevenois, Pieter De Pauw, Steve Schoonooghe, Cédric Delporte, Thami Sebti, Karim Amighi, Serge Muyldermans, Nathalie Wauthoz,

IL-13 is a pleiotropic cytokine mainly secreted by Th2 cells. It reacts with many different types of cells involved in allergy, inflammation, and fibrosis, e.g., mastocytes, B cells, and fibroblasts. The role of IL-13 in conditions involving one or several of these phenotypes has therefore been extensively investigated. The inhibition ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer-BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines.

Sandhya Bansal, Sudhir Perincheri, Timothy Fleming, Christin Poulson, Brian Tiffany, Ross M Bremner, Thalachallour Mohanakumar,

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) causes severe acute respiratory syndrome. mRNA vaccines directed at the SARS-CoV-2 spike protein resulted in development of Abs and protective immunity. To determine the mechanism, we analyzed the kinetics of induction of circulating exosomes with SARS-CoV-2 spike protein and Ab following vaccination ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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Zebrafish prmt2 Attenuates Antiviral Innate Immunity by Targeting traf6.

Junji Zhu, Xiong Li, Xueyi Sun, Ziwen Zhou, Xiaolian Cai, Xing Liu, Jing Wang, Wuhan Xiao,

TNFR-associated factor 6 (TRAF6) not only recruits TBK1/IKKε to MAVS upon virus infection but also catalyzes K63-linked polyubiquitination on substrate or itself, which is critical for NEMO-dependent and -independent TBK1/IKKε activation, leading to the production of type I IFNs. The regulation at the TRAF6 level could affect the activation of ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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The Trypanosome-Derived Metabolite Indole-3-Pyruvate Inhibits Prostaglandin Production in Macrophages by Targeting COX2.

Ciana Diskin, Sarah E Corcoran, Victoria J Tyrrell, Anne F McGettrick, Zbigniew Zaslona, Valerie B O'Donnell, Derek P Nolan, Luke A J O'Neill,

The protozoan parasite <i>Trypanosoma brucei</i> is the causative agent of the neglected tropical disease human African trypanosomiasis, otherwise known as sleeping sickness. Trypanosomes have evolved many immune-evasion mechanisms to facilitate their own survival, as well as prolonging host survival to ensure completion of the parasitic life cycle. A key feature ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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Selective Inhibition of the Interaction between SARS-CoV-2 Spike S1 and ACE2 by SPIDAR Peptide Induces Anti-Inflammatory Therapeutic Responses.

Ramesh K Paidi, Malabendu Jana, Rama K Mishra, Debashis Dutta, Kalipada Pahan,

Many patients with coronavirus disease 2019 in intensive care units suffer from cytokine storm. Although anti-inflammatory therapies are available to treat the problem, very often, these treatments cause immunosuppression. Because angiotensin-converting enzyme 2 (ACE2) on host cells serves as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), to ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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Retroposition of the Long Transcript from Multiexon IFN-β Homologs in Ancestry Vertebrate Gave Rise to the Proximal Transcription Elements of Intronless IFN-β Promoter in Humans.

Shan Nan Chen, Zhen Gan, Pin Nie,

IFN-β is a unique member of type I IFN in humans and contains four positive regulatory domains (PRDs), I-II-III-IV, in its promoter, which are docking sites for transcription factors IFN regulatory factor (IRF) 3/7, NF-κB, IRF3/7, and activating transcription factor 2/Jun proto-oncogene, respectively. In chicken IFN-β and zebrafish IFNφ1 promoters, ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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The Role of Properdin in C5 Convertase Activity and C5b-9 Formation in the Complement Alternative Pathway.

Marloes A H M Michels, Rianne J F Maas, Thea J A M van der Velden, Nicole C A J van de Kar, Lambertus P W J van den Heuvel, Elena B Volokhina, ,

The complement system is an important part of innate immunity. Complement activation leads to formation of convertase enzymes, switch of their specificity from C3 to C5 cleavage, and generation of lytic membrane attack complexes (C5b-9) on surfaces of pathogens. Most C5 cleavage occurs via the complement alternative pathway (AP). The ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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4-Octyl-Itaconate and Dimethyl Fumarate Inhibit COX2 Expression and Prostaglandin Production in Macrophages.

Ciana Diskin, Alessia Zotta, Sarah E Corcoran, Victoria J Tyrrell, Zbigniew Zaslona, Valerie B O'Donnell, Luke A J O'Neill,

PGs are important proinflammatory lipid mediators, the significance of which is highlighted by the widespread and efficacious use of nonsteroidal anti-inflammatory drugs in the treatment of inflammation. 4-Octyl itaconate (4-OI), a derivative of the Krebs cycle-derived metabolite itaconate, has recently garnered much interest as an anti-inflammatory agent. In this article, ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
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Atopic Neutrophils Prevent Postviral Airway Disease.

Syed-Rehan A Hussain, Michelle Rohlfing, Jenny Resiliac, Jennifer Santoro, Mark E Peeples, Dominique Garcin, Mitchell H Grayson,

Respiratory syncytial virus (RSV) infection in infancy is associated with increased risk of asthma, except in those with allergic disease at the time of infection. Using house dust mite allergen, we examined the effect of pre-existing atopy on postviral airway disease using Sendai virus in mice, which models RSV infection ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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Lactoferrin Potentiates Inducible Regulatory T Cell Differentiation through TGF-β Receptor III Binding and Activation of Membrane-Bound TGF-β.

Young-Saeng Jang, Ha-Eon Song, Goo-Young Seo, Hyeon-Ju Jo, Sunhee Park, Hui-Won Park, Tae-Gyu Kim, Seung-Goo Kang, Sung-Il Yoon, Hyun-Jeong Ko, Geun-Shik Lee, Seok-Rae Park, Pyeung-Hyeun Kim,

Lactoferrin (LF) is known to possess anti-inflammatory activity, although its mechanisms of action are not well-understood. The present study asked whether LF affects the commitment of inducible regulatory T cells (Tregs). LF substantially promoted Foxp3 expression by mouse activated CD4<sup>+</sup>T cells, and this activity was further enhanced by TGF-β1. Interestingly, ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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L-PGDS Attenuates Acute Lung Injury by Prostaglandin D2 in Both Dependent and Independent Ways.

Daiki Horikami, Wataru Fujii, Kosuke Aritake, Takahisa Murata,

Lipocalin-type PG D synthase (L-PGDS) has two roles: it can be a PGD synthase, or it can be a carrier protein of hydrophobic small molecules. In this study, we investigated the dual roles of L-PGDS in acute lung injury by using L-PGDS-deficient and point-mutated mice, which lack PGD<sub>2</sub> producibility but ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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Human Cytomegalovirus Infection Promotes Expansion of a Functionally Superior Cytoplasmic CD3+ NK Cell Subset with a Bcl11b-Regulated T Cell Signature.

Zeguang Wu, Colleen M Lau, Rosa Sottile, Jean-Benoît Le Luduec, M Kazim Panjwani, Peter M Conaty, Katja Srpan, Kerstin Laib Sampaio, Thomas Mertens, Stuart P Adler, Ann B Hill, Juliet N Barker, Nai-Kong V Cheung, Joseph C Sun, Katharine C Hsu,

Human CMV (HCMV) is a ubiquitous pathogen that indelibly shapes the NK cell repertoire. Using transcriptomic, epigenomic, and proteomic approaches to evaluate peripheral blood NK cells from healthy human volunteers, we find that prior HCMV infection promotes NK cells with a T cell-like gene profile, including the canonical markers CD3ε, ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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Human-like Response of Pig T Cells to Superagonistic Anti-CD28 Monoclonal Antibodies.

Sabrina Uehlein, Xin Ding, Janina Flößer, Selma Schmidt, Julia Steitz, Maya Bille, Florian Schnitter, Steffen Baltes, Armin Saalmüller, Wilhelm Gerner, Thomas Herrmann, Anna Frey, Thomas Kerkau, Ulrich Hofmann, Niklas Beyersdorf,

Because of its size, anatomical similarities, and now also accessibility to genetic manipulations, pigs are used as animal models for human diseases and immune system development. However, expression and function of CD28, the most important costimulatory receptor expressed by T cells, so far is poorly understood in this species. Using ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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Cutting Edge: Lung-Resident T Cells Elicited by SARS-CoV-2 Do Not Mediate Protection Against Secondary Infection.

Lydia M Roberts, Forrest Jessop, Tara D Wehrly, Catharine M Bosio,

Immunity to pulmonary infection typically requires elicitation of lung-resident T cells that subsequently confer protection against secondary infection. The presence of tissue-resident T cells in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent patients is unknown. Using a sublethal mouse model of coronavirus disease 2019, we determined if SARS-CoV-2 infection ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2021, :]

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SARS-CoV-2-Reactive Mucosal B Cells in the Upper Respiratory Tract of Uninfected Individuals.

Yanling Liu, Patrick Budylowski, Shilan Dong, Zhijie Li, Sofiya Goroshko, Leslie Y T Leung, Eyal Grunebaum, Paolo Campisi, Evan J Propst, Nikolas E Wolter, James M Rini, Amin Zia, Mario Ostrowski, Götz R A Ehrhardt,

SARS-CoV-2 is a respiratory pathogen that can cause severe disease in at-risk populations but results in asymptomatic infections or a mild course of disease in the majority of cases. We report the identification of SARS-CoV-2-reactive B cells in human tonsillar tissue obtained from children who were negative for coronavirus disease ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
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