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Nature Immunology

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https://www.readbyqxmd.com/read/28436956/identification-of-subepithelial-mesenchymal-cells-that-induce-iga-and-diversify-gut-microbiota
#1
Kazuki Nagashima, Shinichiro Sawa, Takeshi Nitta, Masanori Tsutsumi, Tadashi Okamura, Josef M Penninger, Tomoki Nakashima, Hiroshi Takayanagi
Immunoglobulin A (IgA) maintains a symbiotic equilibrium with intestinal microbes. IgA induction in the gut-associated lymphoid tissues (GALTs) is dependent on microbial sampling and cellular interaction in the subepithelial dome (SED). However it is unclear how IgA induction is predominantly initiated in the SED. Here we show that previously unrecognized mesenchymal cells in the SED of GALTs regulate bacteria-specific IgA production and diversify the gut microbiota. Mesenchymal cells expressing the cytokine RANKL directly interact with the gut epithelium to control CCL20 expression and microfold (M) cell differentiation...
April 24, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28436955/vitamin-a-mediates-conversion-of-monocyte-derived-macrophages-into-tissue-resident-macrophages-during-alternative-activation
#2
Uma Mahesh Gundra, Natasha M Girgis, Michael A Gonzalez, Mei San Tang, Hendrik J P Van Der Zande, Jian-Da Lin, Mireille Ouimet, Lily J Ma, Jordan Poles, Nikollaq Vozhilla, Edward A Fisher, Kathryn J Moore, P'ng Loke
It remains unclear whether activated inflammatory macrophages can adopt features of tissue-resident macrophages, or what mechanisms might mediate such a phenotypic conversion. Here we show that vitamin A is required for the phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80(int)CD206(+)PD-L2(+)MHCII(+) macrophages into macrophages with a tissue-resident F4/80(hi)CD206(-)PD-L2(-)MHCII(-)UCP1(+) phenotype in the peritoneal cavity of mice and during the formation of liver granulomas in mice infected with Schistosoma mansoni...
April 24, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28414311/a-self-sustained-loop-of-inflammation-driven-inhibition-of-beige-adipogenesis-in-obesity
#3
Kyoung-Jin Chung, Antonios Chatzigeorgiou, Matina Economopoulou, Ruben Garcia-Martin, Vasileia I Alexaki, Ioannis Mitroulis, Marina Nati, Janine Gebler, Tjalf Ziemssen, Susan E Goelz, Julia Phieler, Jong-Hyung Lim, Katia P Karalis, Thalia Papayannopoulou, Matthias Blüher, George Hajishengallis, Triantafyllos Chavakis
In obesity, inflammation of white adipose tissue (AT) is associated with diminished generation of beige adipocytes ('beige adipogenesis'), a thermogenic and energy-dissipating function mediated by beige adipocytes that express the uncoupling protein UCP1. Here we delineated an inflammation-driven inhibitory mechanism of beige adipogenesis in obesity that required direct adhesive interactions between macrophages and adipocytes mediated by the integrin α4 and its counter-receptor VCAM-1, respectively; expression of the latter was upregulated in obesity...
April 17, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28394372/maintenance-of-the-marginal-zone-b-cell-compartment-specifically-requires-the-rna-binding-protein-zfp36l1
#4
Rebecca Newman, Helena Ahlfors, Alexander Saveliev, Alison Galloway, Daniel J Hodson, Robert Williams, Gurdyal S Besra, Charlotte N Cook, Adam F Cunningham, Sarah E Bell, Martin Turner
RNA-binding proteins of the ZFP36 family are best known for inhibiting the expression of cytokines through binding to AU-rich elements in the 3' untranslated region and promoting mRNA decay. Here we identified an indispensable role for ZFP36L1 as the regulator of a post-transcriptional hub that determined the identity of marginal-zone B cells by promoting their proper localization and survival. ZFP36L1 controlled a gene-expression program related to signaling, cell adhesion and locomotion; it achieved this in part by limiting expression of the transcription factors KLF2 and IRF8, which are known to enforce the follicular B cell phenotype...
April 10, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28369050/antagonism-of-b-cell-enhancer-networks-by-stat5-drives-leukemia-and-poor-patient-survival
#5
Casey D S Katerndahl, Lynn M Heltemes-Harris, Mark J L Willette, Christine M Henzler, Seth Frietze, Rendong Yang, Hilde Schjerven, Kevin A T Silverstein, Laura B Ramsey, Gregory Hubbard, Andrew D Wells, Roland P Kuiper, Blanca Scheijen, Frank N van Leeuwen, Markus Müschen, Steven M Kornblau, Michael A Farrar
The transcription factor STAT5 has a critical role in B cell acute lymphoblastic leukemia (B-ALL). How STAT5 mediates this effect is unclear. Here we found that activation of STAT5 worked together with defects in signaling components of the precursor to the B cell antigen receptor (pre-BCR), including defects in BLNK, BTK, PKCβ, NF-κB1 and IKAROS, to initiate B-ALL. STAT5 antagonized the transcription factors NF-κB and IKAROS by opposing regulation of shared target genes. Super-enhancers showed enrichment for STAT5 binding and were associated with an opposing network of transcription factors, including PAX5, EBF1, PU...
April 3, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28346410/quality-of-tcr-signaling-determined-by-differential-affinities-of-enhancers-for-the-composite-batf-irf4-transcription-factor-complex
#6
Arifumi Iwata, Vivek Durai, Roxane Tussiwand, Carlos G Briseño, Xiaodi Wu, Gary E Grajales-Reyes, Takeshi Egawa, Theresa L Murphy, Kenneth M Murphy
Variable strengths of signaling via the T cell antigen receptor (TCR) can produce divergent outcomes, but the mechanism of this remains obscure. The abundance of the transcription factor IRF4 increases with TCR signal strength, but how this would induce distinct types of responses is unclear. We compared the expression of genes in the TH2 subset of helper T cells to enhancer occupancy by the BATF-IRF4 transcription factor complex at varying strengths of TCR stimulation. Genes dependent on BATF-IRF4 clustered into groups with distinct TCR sensitivities...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28346409/the-metabolic-er-stress-sensor-ire1%C3%AE-suppresses-alternative-activation-of-macrophages-and-impairs-energy-expenditure-in-obesity
#7
Bo Shan, Xiaoxia Wang, Ying Wu, Chi Xu, Zhixiong Xia, Jianli Dai, Mengle Shao, Feng Zhao, Shengqi He, Liu Yang, Mingliang Zhang, Fajun Nan, Jia Li, Jianmiao Liu, Jianfeng Liu, Weiping Jia, Yifu Qiu, Baoliang Song, Jing-Dong J Han, Liangyou Rui, Sheng-Zhong Duan, Yong Liu
Obesity is associated with metabolic inflammation and endoplasmic reticulum (ER) stress, both of which promote metabolic disease progression. Adipose tissue macrophages (ATMs) are key players orchestrating metabolic inflammation, and ER stress enhances macrophage activation. However, whether ER stress pathways underlie ATM regulation of energy homeostasis remains unclear. Here, we identified inositol-requiring enzyme 1α (IRE1α) as a critical switch governing M1-M2 macrophage polarization and energy balance...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28346408/gut-microbial-metabolites-limit-the-frequency-of-autoimmune-t-cells-and-protect-against-type-1-diabetes
#8
Eliana Mariño, James L Richards, Keiran H McLeod, Dragana Stanley, Yu Anne Yap, Jacinta Knight, Craig McKenzie, Jan Kranich, Ana Carolina Oliveira, Fernando J Rossello, Balasubramanian Krishnamurthy, Christian M Nefzger, Laurence Macia, Alison Thorburn, Alan G Baxter, Grant Morahan, Lee H Wong, Jose M Polo, Robert J Moore, Trevor J Lockett, Julie M Clarke, David L Topping, Leonard C Harrison, Charles R Mackay
Gut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon. Each diet provided a high degree of protection from diabetes, even when administered after breakdown of immunotolerance...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28319098/irap-endosomes-restrict-tlr9-activation-and-signaling
#9
Joel Babdor, Delphyne Descamps, Aimé Cézaire Adiko, Mira Tohmé, Sophia Maschalidi, Irini Evnouchidou, Luiz Ricardo Vasconcellos, Mariacristina De Luca, Francois-Xavier Mauvais, Meriem Garfa-Traore, Melanie M Brinkmann, Michel Chignard, Bénédicte Manoury, Loredana Saveanu
The retention of intracellular Toll-like receptors (TLRs) in the endoplasmic reticulum prevents their activation under basal conditions. TLR9 is activated by sensing ligands in specific endosomal-lysosomal compartments. Here we identified IRAP(+) endosomes as major cellular compartments for the early steps of TLR9 activation in dendritic cells (DCs). Both TLR9 and its ligand, the dinucleotide CpG, were present as cargo in IRAP(+) endosomes. In the absence of the aminopeptidase IRAP, the trafficking of CpG and TLR9 to lysosomes and signaling via TLR9 were enhanced in DCs and in mice following bacterial infection...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28319097/long-noncoding-rna-lnckdm2b-is-required-for-ilc3-maintenance-by-initiation-of-zfp292-expression
#10
Benyu Liu, Buqing Ye, Liuliu Yang, Xiaoxiao Zhu, Guanling Huang, Pingping Zhu, Ying Du, Jiayi Wu, Xiwen Qin, Runsheng Chen, Yong Tian, Zusen Fan
Innate lymphoid cells (ILCs) communicate with other hematopoietic and nonhematopoietic cells to regulate immunity, inflammation and tissue homeostasis. How ILC lineages develop and are maintained remains largely unknown. In this study we observed that a divergent long noncoding RNA (lncRNA), lncKdm2b, was expressed at high levels in intestinal group 3 ILCs (ILC3s). LncKdm2b deficiency in the hematopoietic system led to reductions in the number and effector functions of ILC3s. LncKdm2b expression sustained the maintenance of ILC3s by promoting their proliferation through activation of the transcription factor Zfp292...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28288101/opposing-macrophage-polarization-programs-show-extensive-epigenomic-and-transcriptional-cross-talk
#11
Viviana Piccolo, Alessia Curina, Marco Genua, Serena Ghisletti, Marta Simonatto, Arianna Sabò, Bruno Amati, Renato Ostuni, Gioacchino Natoli
Stimulation of macrophages with interferon-γ (IFN-γ) and interleukin 4 (IL-4) triggers distinct and opposing activation programs. During mixed infections or cancer, macrophages are often exposed to both cytokines, but how these two programs influence each other remains unclear. We found that IFN-γ and IL-4 mutually inhibited the epigenomic and transcriptional changes induced by each cytokine alone. Computational and functional analyses revealed the genomic bases for gene-specific cross-repression. For instance, while binding motifs for the transcription factors STAT1 and IRF1 were associated with robust and IL-4-resistant responses to IFN-γ, their coexistence with binding sites for auxiliary transcription factors such as AP-1 generated vulnerability to IL-4-mediated inhibition...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28288100/epigenetic-landscapes-reveal-transcription-factors-that-regulate-cd8-t-cell-differentiation
#12
Bingfei Yu, Kai Zhang, J Justin Milner, Clara Toma, Runqiang Chen, James P Scott-Browne, Renata M Pereira, Shane Crotty, John T Chang, Matthew E Pipkin, Wei Wang, Ananda W Goldrath
Dynamic changes in the expression of transcription factors (TFs) can influence the specification of distinct CD8(+) T cell fates, but the observation of equivalent expression of TFs among differentially fated precursor cells suggests additional underlying mechanisms. Here we profiled the genome-wide histone modifications, open chromatin and gene expression of naive, terminal-effector, memory-precursor and memory CD8(+) T cell populations induced during the in vivo response to bacterial infection. Integration of these data suggested that the expression and binding of TFs contributed to the establishment of subset-specific enhancers during differentiation...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28288099/nlrp12-attenuates-colon-inflammation-by-maintaining-colonic-microbial-diversity-and-promoting-protective-commensal-bacterial-growth
#13
Liang Chen, Justin E Wilson, Mark J Koenigsknecht, Wei-Chun Chou, Stephanie A Montgomery, Agnieszka D Truax, W June Brickey, Christopher D Packey, Nitsan Maharshak, Glenn K Matsushima, Scott E Plevy, Vincent B Young, R Balfour Sartor, Jenny P-Y Ting
Inflammatory bowel diseases involve the dynamic interaction of host genetics, the microbiome and inflammatory responses. Here we found lower expression of NLRP12 (which encodes a negative regulator of innate immunity) in human ulcerative colitis, by comparing monozygotic twins and other patient cohorts. In parallel, Nlrp12 deficiency in mice caused increased basal colonic inflammation, which led to a less-diverse microbiome and loss of protective gut commensal strains (of the family Lachnospiraceae) and a greater abundance of colitogenic strains (of the family Erysipelotrichaceae)...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28263321/social-network-architecture-of-human-immune-cells-unveiled-by-quantitative-proteomics
#14
Jan C Rieckmann, Roger Geiger, Daniel Hornburg, Tobias Wolf, Ksenya Kveler, David Jarrossay, Federica Sallusto, Shai S Shen-Orr, Antonio Lanzavecchia, Matthias Mann, Felix Meissner
The immune system is unique in its dynamic interplay between numerous cell types. However, a system-wide view of how immune cells communicate to protect against disease has not yet been established. We applied high-resolution mass-spectrometry-based proteomics to characterize 28 primary human hematopoietic cell populations in steady and activated states at a depth of >10,000 proteins in total. Protein copy numbers revealed a specialization of immune cells for ligand and receptor expression, thereby connecting distinct immune functions...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28418394/pd-1-targets-cd28
#15
Laurie A Dempsey
No abstract text is available yet for this article.
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28418393/macrophage-dynamics
#16
Ioana Visan
No abstract text is available yet for this article.
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28418392/gene-enhancer-variants-reveal-diverse-tcr-mediated-differentiation
#17
Michael P Gallagher, Leslie J Berg
No abstract text is available yet for this article.
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28418391/vitamin-c-for-microglia
#18
Laurie A Dempsey
No abstract text is available yet for this article.
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28418390/ire1-gives-weight-to-obesity-associated-inflammation
#19
Bojan Bujisic, Fabio Martinon
No abstract text is available yet for this article.
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28418389/the-immune-system-as-a-social-network
#20
Andreas Bergthaler, Jörg Menche
No abstract text is available yet for this article.
April 18, 2017: Nature Immunology
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