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https://www.readbyqxmd.com/read/29565366/erratum-skin-microbiota-host-interactions
#1
Y Erin Chen, Michael A Fischbach, Yasmine Belkaid
This corrects the article DOI: 10.1038/nature25177.
March 21, 2018: Nature
https://www.readbyqxmd.com/read/29414937/c-maf-dependent-regulatory-t-cells-mediate-immunological-tolerance-to-a-gut-pathobiont
#2
Mo Xu, Maria Pokrovskii, Yi Ding, Ren Yi, Christy Au, Oliver J Harrison, Carolina Galan, Yasmine Belkaid, Richard Bonneau, Dan R Littman
Both microbial and host genetic factors contribute to the pathogenesis of autoimmune diseases. There is accumulating evidence that microbial species that potentiate chronic inflammation, as in inflammatory bowel disease, often also colonize healthy individuals. These microorganisms, including the Helicobacter species, can induce pathogenic T cells and are collectively referred to as pathobionts. However, how such T cells are constrained in healthy individuals is not yet understood. Here we report that host tolerance to a potentially pathogenic bacterium, Helicobacter hepaticus, is mediated by the induction of RORγt+ FOXP3+ regulatory T (iTreg ) cells that selectively restrain pro-inflammatory T helper 17 (TH 17) cells and whose function is dependent on the transcription factor c-MAF...
February 15, 2018: Nature
https://www.readbyqxmd.com/read/29382696/contextual-control-of-skin-immunity-and-inflammation-by-corynebacterium
#3
Vanessa K Ridaura, Nicolas Bouladoux, Jan Claesen, Y Erin Chen, Allyson L Byrd, Michael G Constantinides, Eric D Merrill, Samira Tamoutounour, Michael A Fischbach, Yasmine Belkaid
How defined microbes influence the skin immune system remains poorly understood. Here we demonstrate that Corynebacteria , dominant members of the skin microbiota, promote a dramatic increase in the number and activation of a defined subset of γδ T cells. This effect is long-lasting, occurs independently of other microbes, and is, in part, mediated by interleukin (IL)-23. Under steady-state conditions, the impact of Corynebacterium is discrete and noninflammatory. However, when applied to the skin of a host fed a high-fat diet, Corynebacterium accolens alone promotes inflammation in an IL-23-dependent manner...
March 5, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29364878/innate-and-adaptive-lymphocytes-sequentially-shape-the-gut-microbiota-and-lipid-metabolism
#4
Kairui Mao, Antonio P Baptista, Samira Tamoutounour, Lenan Zhuang, Nicolas Bouladoux, Andrew J Martins, Yuefeng Huang, Michael Y Gerner, Yasmine Belkaid, Ronald N Germain
The mammalian gut is colonized by numerous microorganisms collectively termed the microbiota, which have a mutually beneficial relationship with their host. Normally, the gut microbiota matures during ontogeny to a state of balanced commensalism marked by the absence of adverse inflammation. Subsets of innate lymphoid cells (ILCs) and conventional T cells are considered to have redundant functions in containment and clearance of microbial pathogens, but how these two major lymphoid-cell populations each contribute to shaping the mature commensal microbiome and help to maintain tissue homeostasis has not been determined...
February 8, 2018: Nature
https://www.readbyqxmd.com/read/29364286/skin-microbiota-host-interactions
#5
Y Erin Chen, Michael A Fischbach, Yasmine Belkaid
The skin is a complex and dynamic ecosystem that is inhabited by bacteria, archaea, fungi and viruses. These microbes-collectively referred to as the skin microbiota-are fundamental to skin physiology and immunity. Interactions between skin microbes and the host can fall anywhere along the continuum between mutualism and pathogenicity. In this Review, we highlight how host-microbe interactions depend heavily on context, including the state of immune activation, host genetic predisposition, barrier status, microbe localization, and microbe-microbe interactions...
January 24, 2018: Nature
https://www.readbyqxmd.com/read/29358051/non-classical-immunity-controls-microbiota-impact-on-skin-immunity-and-tissue-repair
#6
Jonathan L Linehan, Oliver J Harrison, Seong-Ji Han, Allyson L Byrd, Ivan Vujkovic-Cvijin, Alejandro V Villarino, Shurjo K Sen, Jahangheer Shaik, Margery Smelkinson, Samira Tamoutounour, Nicholas Collins, Nicolas Bouladoux, Amiran Dzutsev, Stephan P Rosshart, Jesse H Arbuckle, Chyung-Ru Wang, Thomas M Kristie, Barbara Rehermann, Giorgio Trinchieri, Jason M Brenchley, John J O'Shea, Yasmine Belkaid
Mammalian barrier surfaces are constitutively colonized by numerous microorganisms. We explored how the microbiota was sensed by the immune system and the defining properties of such responses. Here, we show that a skin commensal can induce T cell responses in a manner that is restricted to non-classical MHC class I molecules. These responses are uncoupled from inflammation and highly distinct from pathogen-induced cells. Commensal-specific T cells express a defined gene signature that is characterized by expression of effector genes together with immunoregulatory and tissue-repair signatures...
February 8, 2018: Cell
https://www.readbyqxmd.com/read/29332945/the-human-skin-microbiome
#7
REVIEW
Allyson L Byrd, Yasmine Belkaid, Julia A Segre
Functioning as the exterior interface of the human body with the environment, skin acts as a physical barrier to prevent the invasion of foreign pathogens while providing a home to the commensal microbiota. The harsh physical landscape of skin, particularly the desiccated, nutrient-poor, acidic environment, also contributes to the adversity that pathogens face when colonizing human skin. Despite this, the skin is colonized by a diverse microbiota. In this Review, we describe amplicon and shotgun metagenomic DNA sequencing studies that have been used to assess the taxonomic diversity of microorganisms that are associated with skin from the kingdom to the strain level...
March 2018: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/29221731/white-adipose-tissue-is-a-reservoir-for-memory-t-cells-and-promotes-protective-memory-responses-to-infection
#8
Seong-Ji Han, Arielle Glatman Zaretsky, Vinicius Andrade-Oliveira, Nicholas Collins, Amiran Dzutsev, Jahangheer Shaik, Denise Morais da Fonseca, Oliver J Harrison, Samira Tamoutounour, Allyson L Byrd, Margery Smelkinson, Nicolas Bouladoux, James B Bliska, Jason M Brenchley, Igor E Brodsky, Yasmine Belkaid
White adipose tissue bridges body organs and plays a fundamental role in host metabolism. To what extent adipose tissue also contributes to immune surveillance and long-term protective defense remains largely unknown. Here, we have shown that at steady state, white adipose tissue contained abundant memory lymphocyte populations. After infection, white adipose tissue accumulated large numbers of pathogen-specific memory T cells, including tissue-resident cells. Memory T cells in white adipose tissue expressed a distinct metabolic profile, and white adipose tissue from previously infected mice was sufficient to protect uninfected mice from lethal pathogen challenge...
December 19, 2017: Immunity
https://www.readbyqxmd.com/read/29139475/intestinal-epithelial-cell-specific-rar%C3%AE-depletion-results-in-aberrant-epithelial-cell-homeostasis-and-underdeveloped-immune-system
#9
H B Jijon, L Suarez-Lopez, O E Diaz, S Das, J De Calisto, M B Yaffe, M J Pittet, J R Mora, Y Belkaid, R J Xavier, E J Villablanca
Retinoic acid (RA), a dietary vitamin A metabolite, is crucial in maintaining intestinal homeostasis. RA acts on intestinal leukocytes to modulate their lineage commitment and function. Although the role of RA has been characterized in immune cells, whether intestinal epithelial cells (IECs) rely on RA signaling to exert their immune-regulatory function has not been examined. Here we demonstrate that lack of RA receptor α (RARα) signaling in IECs results in deregulated epithelial lineage specification, leading to increased numbers of goblet cells and Paneth cells...
November 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29091261/the-mouse-model-of-infection-with-citrobacter-rodentium
#10
Nicolas Bouladoux, Oliver J Harrison, Yasmine Belkaid
Citrobacter rodentium is a murine mucosal pathogen used as a model to elucidate the molecular and cellular pathogenesis of infection with two clinically important human gastrointestinal pathogens, enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC). C. rodentium infection provides an excellent model to study different aspects of host-pathogen interaction in the gut, including intestinal inflammatory responses during bacteria-induced colitis, mucosal healing and epithelial repair, the induction of mucosal immune responses, and the role of the intestinal microbiota in mediating resistance to colonization by enteric pathogens...
November 1, 2017: Current Protocols in Immunology
https://www.readbyqxmd.com/read/28934291/emotional-metacontrol-of-attention-top-down-modulation-of-sensorimotor-processes-in-a-robotic-visual-search-task
#11
Marwen Belkaid, Nicolas Cuperlier, Philippe Gaussier
Emotions play a significant role in internal regulatory processes. In this paper, we advocate four key ideas. First, novelty detection can be grounded in the sensorimotor experience and allow higher order appraisal. Second, cognitive processes, such as those involved in self-assessment, influence emotional states by eliciting affects like boredom and frustration. Third, emotional processes such as those triggered by self-assessment influence attentional processes. Last, close emotion-cognition interactions implement an efficient feedback loop for the purpose of top-down behavior regulation...
2017: PloS One
https://www.readbyqxmd.com/read/28915559/zbtb1-controls-nkp46-ror-gamma-t-innate-lymphoid-cell-ilc3-development
#12
Ying Lu, Xianyu Zhang, Nicolas Bouladoux, Saransh Neel Kaul, Kangxin Jin, Derek Sant'Angelo, Yasmine Belkaid, Damian Kovalovsky
Innate lymphoid cells (ILCs) play a central role conferring protection at the mucosal frontier. In this study, we have identified a requirement of the transcription factor Zbtb1 for the development of RORγt(+) ILCs (ILC3s). Zbtb1-deficient mice lacked NKp46(+) ILC3 cells in the lamina propria of the small and large intestine. This requirement of Zbtb1 was cell intrinsic, as NKp46(+) ILC3s were not generated from Zbtb1-deficient progenitors in bone marrow chimeras and Zbtb1-deficient RORγt(+) CCR6(-)NKp46(-) ILC3s didn't generate NKp46(+) ILC3s in co-cultures with OP9-DL1 stroma...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28778069/zbtb1-controls-nkp46-ror-gamma-t-innate-lymphoid-cell-ilc3-development
#13
Ying Lu, Xianyu Zhang, Nicolas Bouladoux, Saransh Neel Kaul, Kangxin Jin, Derek Sant'Angelo, Yasmine Belkaid, Damian Kovalovsky
Innate lymphoid cells (ILCs) play a central role conferring protection at the mucosal frontier. In this study, we have identified a requirement of the transcription factor Zbtb1 for the development of RORγt+ ILCs (ILC3s). Zbtb1-deficient mice lacked NKp46+ ILC3 cells in the lamina propria of the small and large intestine. This requirement of Zbtb1 was cell intrinsic, as NKp46+ ILC3s were not generated from Zbtb1-deficient progenitors in bone marrow chimeras and Zbtb1-deficient RORγt+ CCR6-NKp46- ILC3s didn't generate NKp46+ ILC3s in co-cultures with OP9-DL1 stroma...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28754678/control-of-regulatory-t-cell-differentiation-by-the-transcription-factors-thpok-and-lrf
#14
Andrea C Carpenter, Elizabeth Wohlfert, Laura B Chopp, Melanie S Vacchio, Jia Nie, Yongmei Zhao, Jyoti Shetty, Qi Xiao, Callie Deng, Bao Tran, Margaret Cam, Matthias M Gaida, Yasmine Belkaid, Rémy Bosselut
The CD4+ lineage-specific transcription factor Thpok is required for intrathymic CD4+ T cell differentiation and, together with its homolog LRF, supports CD4+ T cell helper effector responses. However, it is not known whether these factors are needed for the regulatory T cell (Treg) arm of MHC class II responses. In this study, by inactivating in mice the genes encoding both factors in differentiated Tregs, we show that Thpok and LRF are redundantly required to maintain the size and functions of the postthymic Treg pool...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28679656/-staphylococcus-aureus-and-staphylococcus-epidermidis-strain-diversity-underlying-pediatric-atopic-dermatitis
#15
Allyson L Byrd, Clay Deming, Sara K B Cassidy, Oliver J Harrison, Weng-Ian Ng, Sean Conlan, Yasmine Belkaid, Julia A Segre, Heidi H Kong
The heterogeneous course, severity, and treatment responses among patients with atopic dermatitis (AD; eczema) highlight the complexity of this multifactorial disease. Prior studies have used traditional typing methods on cultivated isolates or sequenced a bacterial marker gene to study the skin microbial communities of AD patients. Shotgun metagenomic sequence analysis provides much greater resolution, elucidating multiple levels of microbial community assembly ranging from kingdom to species and strain-level diversification...
July 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28614804/in-vivo-kinetics-and-nonradioactive-imaging-of-rapidly-proliferating-cells-in-graft-versus-host-disease
#16
Nataliya P Buxbaum, Donald E Farthing, Natella Maglakelidze, Martin Lizak, Hellmut Merkle, Andrea C Carpenter, Brittany U Oliver, Veena Kapoor, Ehydel Castro, Gregory A Swan, Liliane M Dos Santos, Nicolas J Bouladoux, Catherine V Bare, Francis A Flomerfelt, Michael A Eckhaus, William G Telford, Yasmine Belkaid, Remy J Bosselut, Ronald E Gress
Hematopoietic stem cell transplantation (HSCT) offers a cure for cancers that are refractory to chemotherapy and radiation. Most HSCT recipients develop chronic graft-versus-host disease (cGVHD), a systemic alloimmune attack on host organs. Diagnosis is based on clinical signs and symptoms, as biopsies are risky. T cells are central to the biology of cGVHD. We found that a low Treg/CD4+ T effector memory (Tem) ratio in circulation, lymphoid, and target organs identified early and established mouse cGVHD. Using deuterated water labeling to measure multicompartment in vivo kinetics of these subsets, we show robust Tem and Treg proliferation in lymphoid and target organs, while Tregs undergo apoptosis in target organs...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28432130/do-the-microbiota-influence-vaccines-and-protective-immunity-to-pathogens-engaging-our-endogenous-adjuvants
#17
REVIEW
Nicholas Collins, Yasmine Belkaid
The reliance of the immune system on constitutive microbial stimulation support the idea that both responsiveness to vaccines and vaccine design need to be considered in the context of host-microbiota interactions. Manipulation of microbe function or composition via diet alteration or microbiota engraftment may soon become a viable approach to control immunity and, as such, vaccine responses. Learning from our endogenous original adjuvants could be critical in overcoming the enormous hurdle of vaccine design against the numerous pathogens that cause chronic infection...
February 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28423337/homeostatic-immunity-and-the-microbiota
#18
REVIEW
Yasmine Belkaid, Oliver J Harrison
The microbiota plays a fundamental role in the induction, education, and function of the host immune system. In return, the host immune system has evolved multiple means by which to maintain its symbiotic relationship with the microbiota. The maintenance of this dialogue allows the induction of protective responses to pathogens and the utilization of regulatory pathways involved in the sustained tolerance to innocuous antigens. The ability of microbes to set the immunological tone of tissues, both locally and systemically, requires tonic sensing of microbes and complex feedback loops between innate and adaptive components of the immune system...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28414292/dendritic-cells-expressing-immunoreceptor-cd300f-are-critical-for-controlling-chronic-gut-inflammation
#19
Ha-Na Lee, Linjie Tian, Nicolas Bouladoux, Jacquice Davis, Mariam Quinones, Yasmine Belkaid, John E Coligan, Konrad Krzewski
Proinflammatory cytokine overproduction and excessive cell death, coupled with impaired clearance of apoptotic cells, have been implicated as causes of failure to resolve gut inflammation in inflammatory bowel diseases. Here we have found that dendritic cells expressing the apoptotic cell-recognizing receptor CD300f play a crucial role in regulating gut inflammatory responses in a murine model of colonic inflammation. CD300f-deficient mice failed to resolve dextran sulfate sodium-induced colonic inflammation as a result of defects in dendritic cell function that were associated with abnormal accumulation of apoptotic cells in the gut...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28334272/17%C3%AE-estradiol-induced-acsl4-protein-expression-promotes-an-invasive-phenotype-in-estrogen-receptor-positive-mammary-carcinoma-cells
#20
Anissa Belkaid, Rodney J Ouellette, Marc E Surette
Long chain acyl-CoA synthase-4 (ACSL4) expression has been associated with an aggressive phenotype in breast carcinoma cells, whereas its role in ERα-positive breast cancer has not been studied. ACSL4 prefers 20-carbon polyunsaturated fatty acid (PUFA) substrates, and along with other ACSLs has been associated with cellular uptake of exogenous fatty acids. 17β-estradiol induces proliferation and invasive capacities in ERα+ve breast carcinoma that is associated with modifications of cellular lipid metabolism...
April 1, 2017: Carcinogenesis
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