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

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https://www.readbyqxmd.com/read/28807996/klhl6-deficiency-impairs-transitional-b-cell-survival-and-differentiation
#1
Barbara Bertocci, Damiana Lecoeuche, Delphine Sterlin, Julius Kühn, Baptiste Gaillard, Annie De Smet, Frederique Lembo, Christine Bole-Feysot, Nicolas Cagnard, Tatiana Fadeev, Auriel Dahan, Jean-Claude Weill, Claude-Agnès Reynaud
Klhl6 belongs to the KLHL gene family, which is composed of an N-terminal BTB-POZ domain and four to six Kelch motifs in tandem. Several of these proteins function as adaptors of the Cullin3 E3 ubiquitin ligase complex. In this article, we report that Klhl6 deficiency induces, as previously described, a 2-fold reduction in mature B cells. However, we find that this deficit is centered on the inability of transitional type 1 B cells to survive and to progress toward the transitional type 2 B cell stage, whereas cells that have passed this step generate normal germinal centers (GCs) upon a T-dependent immune challenge...
August 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28807995/regulation-of-the-cell-cycle-and-inflammatory-arthritis-by-the-transcription-cofactor-lbh-gene
#2
Shinji Matsuda, Deepa Hammaker, Katharyn Topolewski, Karoline J Briegel, David L Boyle, Steven Dowdy, Wei Wang, Gary S Firestein
Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) display unique aggressive behavior, invading the articular cartilage and promoting inflammation. Using an integrative analysis of RA risk alleles, the transcriptome and methylome in RA FLS, we recently identified the limb bud and heart development (LBH) gene as a key dysregulated gene in RA and other autoimmune diseases. Although some evidence suggests that LBH could modulate the cell cycle, the precise mechanism is unknown and its impact on inflammation in vivo has not been defined...
August 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28807994/a-novel-computational-model-predicts-key-regulators-of-chemokine-gradient-formation-in-lymph-nodes-and-site-specific-roles-for-ccl19-and-ackr4
#3
Mohammad Jafarnejad, David C Zawieja, Bindi S Brook, Robert J B Nibbs, James E Moore
The chemokine receptor CCR7 drives leukocyte migration into and within lymph nodes (LNs). It is activated by chemokines CCL19 and CCL21, which are scavenged by the atypical chemokine receptor ACKR4. CCR7-dependent navigation is determined by the distribution of extracellular CCL19 and CCL21, which form concentration gradients at specific microanatomical locations. The mechanisms underpinning the establishment and regulation of these gradients are poorly understood. In this article, we have incorporated multiple biochemical processes describing the CCL19-CCL21-CCR7-ACKR4 network into our model of LN fluid flow to establish a computational model to investigate intranodal chemokine gradients...
August 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28801359/ccr7-deficiency-allows-accelerated-clearance-of-chlamydia-from-the-female-reproductive-tract
#4
Lin-Xi Li, Jasmine C Labuda, Denise M Imai, Stephen M Griffey, Stephen J McSorley
Immune mechanisms responsible for pathogen clearance from the female reproductive tract (FRT) are incompletely defined; in particular, the contribution of lymphocyte trafficking to this process is unclear. CCR7-deficient mice have profoundly altered lymphocyte recirculation and display ectopic formation of lymphocyte aggregates within mucosal nonlymphoid tissues, including the FRT. In this study, we investigated how altered lymphocyte distribution in CCR7-deficient mice would affect host responses to Chlamydia muridarum within the reproductive tract...
August 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28801358/il-4-il-13-heteroreceptor-influences-th17-cell-conversion-and-sensitivity-to-regulatory-t-cell-suppression-to-restrain-experimental-allergic-encephalomyelitis
#5
Subhasis Barik, Jason S Ellis, Jason A Cascio, Mindy M Miller, Tobechukwu K Ukah, Alexis N Cattin-Roy, Habib Zaghouani
IL-4 and IL-13 have been defined as anti-inflammatory cytokines that can counter myelin-reactive T cells and modulate experimental allergic encephalomyelitis. However, it is not known whether endogenous IL-4 and IL-13 contribute to the maintenance of peripheral tolerance and whether their function is coordinated with T regulatory cells (Tregs). In this study, we used mice in which the common cytokine receptor for IL-4 and IL-13, namely the IL-4Rα/IL-13Rα1 (13R) heteroreceptor (HR), is compromised and determined whether the lack of signaling by endogenous IL-4 and IL-13 through the HR influences the function of effector Th1 and Th17 cells in a Treg-dependent fashion...
August 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28801357/the-autoimmune-risk-variant-ptpn22-c1858t-alters-b-cell-tolerance-at-discrete-checkpoints-and-differentially-shapes-the-naive-repertoire
#6
Genita Metzler, Xuezhi Dai, Christopher D Thouvenel, Socheath Khim, Tania Habib, Jane H Buckner, David J Rawlings
A common genetic variant in the gene encoding the protein tyrosine phosphatase nonreceptor type 22 (PTPN22 C1858T) has been linked to a wide range of autoimmune disorders. Although a B cell-intrinsic role in promoting disease has been reported, the mechanism(s) through which this variant functions to alter the preimmune B cell repertoire remains unknown. Using a series of polyclonal and transgenic self-reactive models harboring the analogous mutation in murine Ptpn22, we show evidence for enhanced BCR, B cell-activating factor receptor, and CD40 coreceptor programs, leading to broadly enhanced positive selection of B cells at two discrete checkpoints in the bone marrow and spleen...
August 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28794235/integrin-linked-kinase-expression-in-myeloid-cells-promotes-inflammatory-signaling-during-experimental-colitis
#7
Afsar U Ahmed, Howard C H Yim, Mariah Alorro, Matthias Ernst, Bryan R G Williams
The pathology of inflammatory bowel diseases is driven by the inflammatory signaling pathways associated with mucosal epithelial damage. Myeloid cells are known to play an essential role in mediating epithelial inflammatory responses during injury. However, the precise role of these cells in stimulating intestinal inflammation and the subsequent tissue damage is unclear. In this article, we show that expression of integrin-linked kinase (ILK) in myeloid cells is critical for the epithelial inflammatory signaling during colitis induced by dextran sodium sulfate...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28794234/deep-immune-profiling-of-an-arginine-enriched-nutritional-intervention-in-patients-undergoing-surgery
#8
Nima Aghaeepour, Cindy Kin, Edward A Ganio, Kent P Jensen, Dyani K Gaudilliere, Martha Tingle, Amy Tsai, Hope L Lancero, Benjamin Choisy, Leslie S McNeil, Robin Okada, Andrew A Shelton, Garry P Nolan, Martin S Angst, Brice L Gaudilliere
Application of high-content immune profiling technologies has enormous potential to advance medicine. Whether these technologies reveal pertinent biology when implemented in interventional clinical trials is an important question. The beneficial effects of preoperative arginine-enriched dietary supplements (AES) are highly context specific, as they reduce infection rates in elective surgery, but possibly increase morbidity in critically ill patients. This study combined single-cell mass cytometry with the multiplex analysis of relevant plasma cytokines to comprehensively profile the immune-modifying effects of this much-debated intervention in patients undergoing surgery...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28794233/characterization-of-mycobacterium-tuberculosis-specific-cells-using-mhc-class-ii-tetramers-reveals-phenotypic-differences-related-to-hiv-infection-and-tuberculosis-disease
#9
Natalie Strickland, Tracey L Müller, Natacha Berkowitz, Rene Goliath, Mary N Carrington, Robert J Wilkinson, Wendy A Burgers, Catherine Riou
A major challenge for the development of an effective vaccine against tuberculosis (TB) is that the attributes of protective CD4(+) T cell responses are still elusive for human TB. Infection with HIV type 1 is a major risk factor for TB, and a better understanding of HIV-induced alterations of Mycobacterium tuberculosis-specific CD4(+) T cells that leads to failed host resistance may provide insight into protective T cell immunity to TB. A total of 86 participants from a TB-endemic setting, either HIV-infected or uninfected and with latent or active TB (aTB), were screened using M...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28794232/resolvin-d1-improves-the-resolution-of-inflammation-via-activating-nf-%C3%AE%C2%BAb-p50-p50-mediated-cyclooxygenase-2-expression-in-acute-respiratory-distress-syndrome
#10
Ye Gao, Huawei Zhang, Lingchun Luo, Jing Lin, Dan Li, Sisi Zheng, Hua Huang, Songfan Yan, Jingxiang Yang, Yu Hao, Hui Li, Fang Gao Smith, Shengwei Jin
Acute respiratory distress syndrome (ARDS) is a severe illness characterized by uncontrolled inflammation. The resolution of inflammation is a tightly regulated event controlled by endogenous mediators, such as resolvin D1 (RvD1). Cyclooxygenase-2 (COX-2) has been reported to promote inflammation, along with PGE2, in the initiation of inflammation, as well as in prompting resolution, with PGD2 acting in the later phase of inflammation. Our previous work demonstrated that RvD1 enhanced COX-2 and PGD2 expression to resolve inflammation...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28794231/cutting-edge-murine-nk-cells-degranulate-and-retain-cytotoxic-function-without-store-operated-calcium-entry
#11
Jacquelyn Freund-Brown, Ruth Choa, Brenal K Singh, Tanner Ford Robertson, Gabrielle M Ferry, Eric Viver, Hamid Bassiri, Janis K Burkhardt, Taku Kambayashi
Sustained Ca(2+) signaling, known as store-operated calcium entry (SOCE), occurs downstream of immunoreceptor engagement and is critical for cytotoxic lymphocyte signaling and effector function. CD8(+) T cells require sustained Ca(2+) signaling for inflammatory cytokine production and the killing of target cells; however, much less is known about its role in NK cells. In this study, we use mice deficient in stromal interacting molecules 1 and 2, which are required for SOCE, to examine the contribution of sustained Ca(2+) signaling to murine NK cell function...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28794230/analysis-of-factor-d-isoforms-in-malpuech-michels-mingarelli-carnevale-patients-highlights-the-role-of-masp-3-as-a-maturase-in-the-alternative-pathway-of-complement
#12
Rasmus Pihl, Lisbeth Jensen, Annette G Hansen, Ida B Thøgersen, Stephanie Andres, Frederik Dagnæs-Hansen, Konrad Oexle, Jan J Enghild, Steffen Thiel
Factor D (FD), which is also known as adipsin, is regarded as the first-acting protease of the alternative pathway (AP) of complement. It has been suggested that FD is secreted as a mature enzyme that does not require subsequent activation. This view was challenged when it was shown that mice lacking mannose-binding lectin (MBL)-associated serine protease-1 (MASP-1) and MASP-3 contain zymogenic FD (pro-FD), and it is becoming evident that MASP-3 is implicated in pro-FD maturation. However, the necessity of MASP-3 for pro-FD cleavage has been questioned, because AP activity is still observed in sera from MASP-1/3-deficient Malpuech-Michels-Mingarelli-Carnevale (3MC) patients...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28794229/dock8-drives-src-dependent-nk-cell-effector-function
#13
Conor J Kearney, Stephin J Vervoort, Kelly M Ramsbottom, Andrew J Freeman, Jessica Michie, Jane Peake, Jean-Laurent Casanova, Capucine Picard, Stuart G Tangye, Cindy S Ma, Ricky W Johnstone, Katrina L Randall, Jane Oliaro
Mutations in the dedicator of cytokinesis 8 (DOCK8) gene cause an autosomal recessive form of hyper-IgE syndrome, characterized by chronic immunodeficiency with persistent microbial infection and increased incidence of malignancy. These manifestations suggest a defect in cytotoxic lymphocyte function and immune surveillance. However, how DOCK8 regulates NK cell-driven immune responses remains unclear. In this article, we demonstrate that DOCK8 regulates NK cell cytotoxicity and cytokine production in response to target cell engagement or receptor ligation...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28784848/cutting-edge-il-2-induced-expression-of-the-amino-acid-transporters-slc1a5-and-cd98-is-a-prerequisite-for-nkg2d-mediated-activation-of-human-nk-cells
#14
Helle Jensen, Marc Potempa, Dagmar Gotthardt, Lewis L Lanier
Priming of human NK cells with IL-2 is necessary to render them functionally competent upon NKG2D engagement. We examined the underlying mechanisms that control NKG2D responsiveness in NK cells and found that IL-2 upregulates expression of the amino acid transporters SLC1A5 and CD98. Using specific inhibitors to block SLC1A5 and CD98 function, we found that production of IFN-γ and degranulation by CD56(bright) and CD56(dim) NK cells following NKG2D stimulation were dependent on both transporters. IL-2 priming increased the activity of mTORC1, and inhibition of mTORC1 abrogated the ability of the IL-2-primed NK cells to produce IFN-γ in response to NKG2D-mediated stimulation...
August 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28784847/%C3%AE-3-deletion-isoform-of-hla-a11-modulates-cytotoxicity-of-nk-cells-correlations-with-hiv-1-infection-of-cells
#15
Xi-He Zhang, Xiao-Dong Lian, Zheng-Xi Dai, Hong-Yi Zheng, Xin Chen, Yong-Tang Zheng
Alternative splicing occurs frequently in many genes, especially those involved in immunity. Unfortunately, the functions of many alternatively spliced molecules from immunologically relevant genes remain unknown. Classical HLA-I molecules are expressed on almost all nucleated cells and play a pivotal role in both innate and adaptive immunity. Although splice variants of HLA-I genes have been reported, the details of their functions have not been reported. In the current study, we determined the characteristics, expression, and function of a novel splice variant of HLA-A11 named HLA-A11svE4 HLA-A11svE4 is located on the cell surface without β2-microglobulin (β2m)...
August 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28784846/dectin-1-activation-during-leishmania-amazonensis-phagocytosis-prompts-syk-dependent-reactive-oxygen-species-production-to-trigger-inflammasome-assembly-and-restriction-of-parasite-replication
#16
Djalma S Lima-Junior, Tiago W P Mineo, Vera L G Calich, Dario S Zamboni
Protozoan parasites of the genus Leishmania are the causative agents of Leishmaniasis, a disease that can be lethal and affects 12 million people worldwide. Leishmania replicates intracellularly in macrophages, a process that is essential for disease progression. Although the production of reactive oxygen species (ROS) accounts for restriction of parasite replication, Leishmania is known to induce ROS upon macrophage infection. We have recently demonstrated NLRP3 inflammasome activation in infected macrophages, a process that is important for the outcome of infection...
August 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28784845/oxidized-low-density-lipoprotein-loading-of-macrophages-downregulates-tlr-induced-proinflammatory-responses-in-a-gene-specific-and-temporal-manner-through-transcriptional-control
#17
Jenny Jongstra-Bilen, Cindy X Zhang, Timothy Wisnicki, Mengyi K Li, Samantha White-Alfred, Ragave Ilaalagan, Dario M Ferri, Ashley Deonarain, Mark H Wan, Sharon J Hyduk, Carolyn L Cummins, Myron I Cybulsky
Hypercholesterolemia is a key risk factor for atherosclerosis and leads to the uptake of native and oxidized low-density lipoprotein (oxLDL) by macrophages (Mϕs) and foam cell formation. Inflammatory processes accompany Mϕ foam cell formation in the artery wall, yet the relationship between Mϕ lipid loading and their response to inflammatory stimuli remains elusive. We investigated proinflammatory gene expression in thioglycollate-elicited peritoneal Mϕs, bone marrow-derived Mϕs and dendritic cells, and RAW264...
August 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28784844/il-33-signaling-regulates-innate-il-17a-and-il-22-production-via-suppression-of-prostaglandin-e2-during-lung-fungal-infection
#18
Jaleesa M Garth, Kristen M Reeder, Matthew S Godwin, Joseph J Mackel, Chad W Dunaway, Jonathan P Blackburn, Chad Steele
Members of the IL-1 family play protective and regulatory roles in immune defense against the opportunistic mold Aspergillus fumigatus In this study, we investigated the IL-1 family member IL-33 in lung defense against A. fumigatus IL-33 was detected in the naive lung, which further increased after exposure to A. fumigatus in a dectin-1-independent manner. Mice deficient in the receptor for IL-33 (Il1rl1(-/-)) unexpectedly demonstrated enhanced lung clearance of A. fumigatus IL-33 functioned as a negative regulator of multiple inflammatory cytokines, as IL-1α, IL-1β, IL-6, IL-17A, and IL-22 were significantly elevated in fungal-exposed Il1rl1(-/-) mice...
August 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28779024/macrophages-induce-long-term-trapping-of-%C3%AE-%C3%AE-t-cells-with-innate-like-properties-within-secondary-lymphoid-organs-in-the-steady-state
#19
Alexandra Audemard-Verger, Matthieu Rivière, Aurélie Durand, Elisa Peranzoni, Vincent Guichard, Pauline Hamon, Nelly Bonilla, Thomas Guilbert, Alexandre Boissonnas, Cédric Auffray, Gérard Eberl, Bruno Lucas, Bruno Martin
So far, peripheral T cells have mostly been described to circulate between blood, secondary lymphoid organs (SLOs), and lymph in the steady state. This nomadic existence would allow them to accomplish their surveying task for both foreign Ags and survival signals. Although it is now well established that γδ T cells can be rapidly recruited to inflammatory sites or in certain tumor microenvironments, the trafficking properties of peripheral γδ T cells have been poorly studied in the steady state. In the present study, we highlight the existence of resident γδ T cells in the SLOs of specific pathogen-free mice...
August 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28779023/notch-balances-th17-and-induced-regulatory-t-cell-functions-in-dendritic-cells-by-regulating-aldh1a2-expression
#20
Taskia Sultana Zaman, Hideki Arimochi, Satoshi Maruyama, Chieko Ishifune, Shin-Ichi Tsukumo, Akiko Kitamura, Koji Yasutomo
Dendritic cells (DCs) are important for adaptive immune responses through the activation of T cells. The molecular interplay between DCs and T cells determines the magnitude of T cell responses or outcomes of functional differentiation of T cells. In this study, we demonstrated that DCs in mice that are Rbpj deficient in CD11c(+) cells (Rbpj(-/-) mice) promoted the differentiation of IL-17A-producing Th17 cells. Rbpj-deficient DCs expressed little Aldh1a2 protein that is required for generating retinoic acid...
August 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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