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Immunity

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https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#1
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28214225/a-relay-pathway-between-arginine-and-tryptophan-metabolism-confers-immunosuppressive-properties-on-dendritic-cells
#2
Giada Mondanelli, Roberta Bianchi, Maria Teresa Pallotta, Ciriana Orabona, Elisa Albini, Alberta Iacono, Maria Laura Belladonna, Carmine Vacca, Francesca Fallarino, Antonio Macchiarulo, Stefano Ugel, Vincenzo Bronte, Federica Gevi, Lello Zolla, Auke Verhaar, Maikel Peppelenbosch, Emilia Maria Cristina Mazza, Silvio Bicciato, Yasmina Laouar, Laura Santambrogio, Paolo Puccetti, Claudia Volpi, Ursula Grohmann
Arginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunoregulatory enzymes catalyzing the degradation of l-arginine and l-tryptophan, respectively, resulting in local amino acid deprivation. In addition, unlike Arg1, IDO1 is also endowed with non-enzymatic signaling activity in dendritic cells (DCs). Despite considerable knowledge of their individual biology, no integrated functions of Arg1 and IDO1 have been reported yet. We found that IDO1 phosphorylation and consequent activation of IDO1 signaling in DCs was strictly dependent on prior expression of Arg1 and Arg1-dependent production of polyamines...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28190711/cd8-t-cells-orchestrate-pdc-xcr1-dendritic-cell-spatial-and-functional-cooperativity-to-optimize-priming
#3
Anna Brewitz, Sarah Eickhoff, Sabrina Dähling, Thomas Quast, Sammy Bedoui, Richard A Kroczek, Christian Kurts, Natalio Garbi, Winfried Barchet, Matteo Iannacone, Frederick Klauschen, Waldemar Kolanus, Tsuneyasu Kaisho, Marco Colonna, Ronald N Germain, Wolfgang Kastenmüller
Adaptive cellular immunity is initiated by antigen-specific interactions between T lymphocytes and dendritic cells (DCs). Plasmacytoid DCs (pDCs) support antiviral immunity by linking innate and adaptive immune responses. Here we examined pDC spatiotemporal dynamics during viral infection to uncover when, where, and how they exert their functions. We found that pDCs accumulated at sites of CD8(+) T cell antigen-driven activation in a CCR5-dependent fashion. Furthermore, activated CD8(+) T cells orchestrated the local recruitment of lymph node-resident XCR1 chemokine receptor-expressing DCs via secretion of the XCL1 chemokine...
February 8, 2017: Immunity
https://www.readbyqxmd.com/read/28228285/mass-spectrometry-profiling-of-hla-associated-peptidomes-in-mono-allelic-cells-enables-more-accurate-epitope-prediction
#4
Jennifer G Abelin, Derin B Keskin, Siranush Sarkizova, Christina R Hartigan, Wandi Zhang, John Sidney, Jonathan Stevens, William Lane, Guang Lan Zhang, Thomas M Eisenhaure, Karl R Clauser, Nir Hacohen, Michael S Rooney, Steven A Carr, Catherine J Wu
Identification of human leukocyte antigen (HLA)-bound peptides by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is poised to provide a deep understanding of rules underlying antigen presentation. However, a key obstacle is the ambiguity that arises from the co-expression of multiple HLA alleles. Here, we have implemented a scalable mono-allelic strategy for profiling the HLA peptidome. By using cell lines expressing a single HLA allele, optimizing immunopurifications, and developing an application-specific spectral search algorithm, we identified thousands of peptides bound to 16 different HLA class I alleles...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228284/respiratory-syncytial-virus-infects-regulatory-b-cells-in-human-neonates-via-chemokine-receptor-cx3cr1-and-promotes-lung-disease-severity
#5
Dania Zhivaki, Sébastien Lemoine, Annick Lim, Ahsen Morva, Pierre-Olivier Vidalain, Liliane Schandene, Nicoletta Casartelli, Marie-Anne Rameix-Welti, Pierre-Louis Hervé, Edith Dériaud, Benoit Beitz, Maryline Ripaux-Lefevre, Jordi Miatello, Brigitte Lemercier, Valerie Lorin, Delphyne Descamps, Jenna Fix, Jean-François Eléouët, Sabine Riffault, Olivier Schwartz, Fabrice Porcheray, Françoise Mascart, Hugo Mouquet, Xiaoming Zhang, Pierre Tissières, Richard Lo-Man
Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants and is characterized by pulmonary infiltration of B cells in fatal cases. We analyzed the B cell compartment in human newborns and identified a population of neonatal regulatory B lymphocytes (nBreg cells) that produced interleukin 10 (IL-10) in response to RSV infection. The polyreactive B cell receptor of nBreg cells interacted with RSV protein F and induced upregulation of chemokine receptor CX3CR1. CX3CR1 interacted with RSV glycoprotein G, leading to nBreg cell infection and IL-10 production that dampened T helper 1 (Th1) cytokine production...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228283/adipose-type-one-innate-lymphoid-cells-regulate-macrophage-homeostasis-through-targeted-cytotoxicity
#6
Selma Boulenouar, Xavier Michelet, Danielle Duquette, David Alvarez, Andrew E Hogan, Christina Dold, Donal O'Connor, Suzanne Stutte, Ali Tavakkoli, Desmond Winters, Mark A Exley, Donal O'Shea, Michael B Brenner, Ulrich von Andrian, Lydia Lynch
Adipose tissue has a dynamic immune system that adapts to changes in diet and maintains homeostatic tissue remodeling. Adipose type 1 innate lymphoid cells (AT1-ILCs) promote pro-inflammatory macrophages in obesity, but little is known about their functions at steady state. Here we found that human and murine adipose tissue harbor heterogeneous populations of AT1-ILCs. Experiments using parabiotic mice fed a high-fat diet (HFD) showed differential trafficking of AT1-ILCs, particularly in response to short- and long-term HFD and diet restriction...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228282/complement-factor-h-inhibits-cd47-mediated-resolution-of-inflammation
#7
Bertrand Calippe, Sebastien Augustin, Fanny Beguier, Hugo Charles-Messance, Lucie Poupel, Jean-Baptiste Conart, Shulong J Hu, Sophie Lavalette, Alexandre Fauvet, Julie Rayes, Olivier Levy, William Raoul, Catherine Fitting, Thomas Denèfle, Matthew C Pickering, Claire Harris, Sylvie Jorieux, Patrick M Sullivan, José-Alain Sahel, Philippe Karoyan, Przemyslaw Sapieha, Xavier Guillonneau, Emmanuel L Gautier, Florian Sennlaub
Variants of the CFH gene, encoding complement factor H (CFH), show strong association with age-related macular degeneration (AMD), a major cause of blindness. Here, we used murine models of AMD to examine the contribution of CFH to disease etiology. Cfh deletion protected the mice from the pathogenic subretinal accumulation of mononuclear phagocytes (MP) that characterize AMD and showed accelerated resolution of inflammation. MP persistence arose secondary to binding of CFH to CD11b, which obstructed the homeostatic elimination of MPs from the subretinal space mediated by thrombospsondin-1 (TSP-1) activation of CD47...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228281/dysregulation-of-the-cytokine-gm-csf-induces-spontaneous-phagocyte-invasion-and-immunopathology-in-the-central-nervous-system
#8
Sabine Spath, Juliana Komuczki, Mario Hermann, Pawel Pelczar, Florian Mair, Bettina Schreiner, Burkhard Becher
Chronic inflammatory diseases are influenced by dysregulation of cytokines. Among them, granulocyte macrophage colony stimulating factor (GM-CSF) is crucial for the pathogenic function of T cells in preclinical models of autoimmunity. To study the impact of dysregulated GM-CSF expression in vivo, we generated a transgenic mouse line allowing the induction of GM-CSF expression in mature, peripheral helper T (Th) cells. Antigen-independent GM-CSF release led to the invasion of inflammatory myeloid cells into the central nervous system (CNS), which was accompanied by the spontaneous development of severe neurological deficits...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228280/autocrine-loop-involving-il-6-family-member-lif-lif-receptor-and-stat4-drives-sustained-fibroblast-production-of-inflammatory-mediators
#9
Hung N Nguyen, Erika H Noss, Fumitaka Mizoguchi, Christine Huppertz, Kevin S Wei, Gerald F M Watts, Michael B Brenner
Fibroblasts are major contributors to and regulators of inflammation and dominant producers of interleukin-6 (IL-6) in inflammatory diseases like rheumatoid arthritis. Yet, compared to leukocytes, the regulation of inflammatory pathways in fibroblasts is largely unknown. Here, we report that analyses of genes coordinately upregulated with IL-6 pointed to STAT4 and leukemia inhibitory factor (LIF) as potentially linked. Gene silencing revealed that STAT4 was required for IL-6 transcription. STAT4 was recruited to the IL-6 promoter after fibroblast activation, and LIF receptor (LIFR) and STAT4 formed a molecular complex that, together with JAK1 and TYK2 kinases, controlled STAT4 activation...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228279/loss-of-pten-is-associated-with-resistance-to-anti-pd-1-checkpoint-blockade-therapy-in-metastatic-uterine-leiomyosarcoma
#10
Suzanne George, Diana Miao, George D Demetri, Dennis Adeegbe, Scott J Rodig, Sachet Shukla, Mikel Lipschitz, Ali Amin-Mansour, Chandrajit P Raut, Scott L Carter, Peter Hammerman, Gordon J Freeman, Catherine J Wu, Patrick A Ott, Kwok-Kin Wong, Eliezer M Van Allen
Response to immune checkpoint blockade in mesenchymal tumors is poorly characterized, but immunogenomic dissection of these cancers could inform immunotherapy mediators. We identified a treatment-naive patient who has metastatic uterine leiomyosarcoma and has experienced complete tumor remission for >2 years on anti-PD-1 (pembrolizumab) monotherapy. We analyzed the primary tumor, the sole treatment-resistant metastasis, and germline tissue to explore mechanisms of immunotherapy sensitivity and resistance...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228278/immunopathogenesis-of-rheumatoid-arthritis
#11
REVIEW
Gary S Firestein, Iain B McInnes
Rheumatoid arthritis (RA) is the most common inflammatory arthropathy. The majority of evidence, derived from genetics, tissue analyses, models, and clinical studies, points to an immune-mediated etiology associated with stromal tissue dysregulation that together propogate chronic inflammation and articular destruction. A pre-RA phase lasting months to years may be characterized by the presence of circulating autoantibodies, increasing concentration and range of inflammatory cytokines and chemokines, and altered metabolism...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228277/prospects-for-a-zika-virus-vaccine
#12
REVIEW
Dan H Barouch, Stephen J Thomas, Nelson L Michael
A recent unprecedented outbreak of Zika virus (ZIKV) in the Americas has been associated with microcephaly and other congenital malformations in infants as well as Guillain-Barre syndrome in adults. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Promising data from preclinical vaccine studies in mice and monkeys suggest that an effective vaccine will likely be possible, but important scientific challenges remain. Here we review the current state of ZIKV vaccine development...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228276/the-dark-age-ing-of-the-inflammasome
#13
Konrad Aden, Philip Rosenstiel
Mechanisms that contribute to healthy aging remain obscure. In a recent issue of Nature Medicine, Furman et al. (2017) describe that dietary caffeine inhibits the NLRC4 inflammasome, which is associated with disease-free aging.
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228275/rsv-takes-control-of-neonatal-breg-cells-two-hands-on-the-wheel
#14
Peter J M Openshaw
The viral attachment protein of RSV has many surprising features, especially its mimicry of fractalkine (CX3CL1). Zhivaki et al. (2017) now show that, in addition to using this homology to attach to ciliated cells, it activates human neonatal regulatory B cells, thereby inhibiting immunological responses.
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228274/killer-ilcs-in-the-fat
#15
Emilie Narni-Mancinelli, Eric Vivier
Innate lymphoid cells (ILCs) residing in adipose tissue participate in the pathogenesis of obesity, but their contribution toward adipose tissue homeostasis in the lean state is unclear. Boulenouar et al. (2017) now report that heterogenous type 1 ILCs in adipose tissues regulate macrophage homeostasis through cytotoxicity.
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228273/compliments-of-factor-h-what-s-in-it-for-amd
#16
Mary J Mattapallil, Rachel R Caspi
Genetic variations in complement factor H (CFH) confer greater risk for age-related macular degeneration (AMD). In this issue of Immunity, Calippe et al. (2017) uncover a non-canonical role for CFH in the inhibition of mononuclear phagocyte elimination from sub-retinal lesions, providing insight into the pathophysiology of AMD associated with CFH variants.
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228272/commanding-cns-invasion-gm-csf
#17
Junjie Zhao, Lillian Sun, Xiaoxia Li
Granulocyte-macrophage colony-stimulating factor (GM-CSF or Csf-2) is a pro-inflammatory mediator implicated in the pathogenesis of various autoimmune diseases. In this issue of Immunity, Spath et al. (2017) show that the dysregulated production of GM-CSF rather than IL-17 induces spontaneous immunopathology in a mouse model of CNS inflammation.
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228271/antigen-primed-cd8-t-cells-call-dcs-for-back-up
#18
Marianne Burbage, Sebastian Amigorena
Encounters between naive T lymphocytes and dendritic cells (DCs) bearing adequate co-stimulatory signals are rare. In this issue of Immunity, Brewitz et al. (2017) show that chemokines secreted by CD8(+) T cells recruit myeloid and plasmacytoid DCs that in turn boost CD8(+) T cell activation.
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28099867/th17-cells-require-you-to-chew-before-you-swallow
#19
Marc Veldhoen
How immunity is regulated at distinct epithelial tissues that vary in microbial occupancy and environmental and tissue specific cues isn't clear. Dutzan et al. (2017) report that mechanical-derived signals, not those from micro-organisms, are key to maintaining interleukin-17-expressing T helper (Th17) cells at the oral epithelia.
January 17, 2017: Immunity
https://www.readbyqxmd.com/read/28099866/effector-regulatory-t-cell-differentiation-and-immune-homeostasis-depend-on-the-transcription-factor-myb
#20
Sheila Dias, Angela D'Amico, Erika Cretney, Yang Liao, Julie Tellier, Christine Bruggeman, Francisca F Almeida, Jamie Leahy, Gabrielle T Belz, Gordon K Smyth, Wei Shi, Stephen L Nutt
FoxP3-expressing regulatory T (Treg) cells are essential for maintaining immune homeostasis. Activated Treg cells undergo further differentiation into an effector state that highly expresses genes critical for Treg cell function, although how this process is coordinated on a transcriptional level is poorly understood. Here, we demonstrate that mice lacking the transcription factor Myb in Treg cells succumbed to a multi-organ inflammatory disease. Myb was specifically expressed in, and required for the differentiation of, thymus-derived effector Treg cells...
January 17, 2017: Immunity
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