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5 results on '"MESH: RNA, Messenger / genetics"'

1. Fgf8 dynamics and critical slowing down may account for the temperature independence of somitogenesis

Author

Weiting Zhang, Pierluigi Scerbo, Marine Delagrange, Virginie Candat, Vanessa Mayr, Sophie Vriz, Martin Distel, Bertrand Ducos, David Bensimon, ABCD : Biophysique des Biomolécules, Laboratoire de physique de l'ENS - ENS Paris (LPENS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), St. Anna Children’s Cancer Research Institute CCRI [Vienna], Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Chemistry and Biochemistry [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), ANR-10-LABX-0054,MEMOLIFE,Memory in living systems: an integrated approach(2010), VERZIER, Anne-Cécile, and Memory in living systems: an integrated approach - - MEMOLIFE2010 - ANR-10-LABX-0054 - LABX - VALID

Subjects
MESH: Fibroblast Growth Factor 8 / metabolism, animal structures, Embryo, Nonmammalian, Fibroblast Growth Factor 8, QH301-705.5, MESH: p-Aminoazobenzene / pharmacology, [SDV]Life Sciences [q-bio], Embryonic Development, Medicine (miscellaneous), MESH: Embryonic Development / physiology, MESH: Embryonic Development / genetics, General Biochemistry, Genetics and Molecular Biology, [PHYS] Physics [physics], MESH: Embryo, Nonmammalian / metabolism, MESH: Fibroblast Growth Factor 8 / genetics, MESH: Gene Expression Regulation, Developmental / physiology, Animals, MESH: Animals, RNA, Messenger, Biology (General), MESH: p-Aminoazobenzene / analogs & derivatives, MESH: Zebrafish, Zebrafish, [PHYS]Physics [physics], Body patterning, MESH: RNA, Messenger / metabolism, Gene Expression Regulation, Developmental, [SDV] Life Sciences [q-bio], stomatognathic diseases, Embryonic induction, p-Aminoazobenzene, embryonic structures, MESH: RNA, Messenger / genetics, General Agricultural and Biological Sciences
Abstract

Somitogenesis, the segmentation of the antero-posterior axis in vertebrates, is thought to result from the interactions between a genetic oscillator and a posterior-moving determination wavefront. The segment (somite) size is set by the product of the oscillator period and the velocity of the determination wavefront. Surprisingly, while the segmentation period can vary by a factor three between 20 °C and 32 °C, the somite size is constant. How this temperature independence is achieved is a mystery that we address in this study. Using RT-qPCR we show that the endogenous fgf8 mRNA concentration decreases during somitogenesis and correlates with the exponent of the shrinking pre-somitic mesoderm (PSM) size. As the temperature decreases, the dynamics of fgf8 and many other gene transcripts, as well as the segmentation frequency and the PSM shortening and tail growth rates slows down as T–Tc (with Tc = 14.4 °C). This behavior characteristic of a system near a critical point may account for the temperature independence of somitogenesis in zebrafish.

Published
2022

2. Small-RNA-mediated transgenerational silencing of histone genes impairs fertility in piRNA mutants

Author

Blaise Li, Martino Ugolini, Damarys Loew, Germano Cecere, Aleksei Samolygo, Céline Didier, Eric Cornes, Meetali Singh, Giorgia Barucci, Piergiuseppe Quarato, Florent Dingli, Mécanismes de l'Hérédité épigénétique / Mechanisms of epigenetic inheritance, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Scuola Normale Superiore di Pisa (SNS), Moscow Institute of Physics and Technology [Moscow] (MIPT), Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie [Paris], This project has received funding from the Institut Pasteur, the CNRS and the European Research Council (ERC) under the EU Horizon 2020 research and innovation programme under grant agreement no. ERC-StG- 679243. G.B. is part of the Pasteur–Paris University (PPU) International PhD Program and has received funding from the EU Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 665807. E.C. was supported by a Pasteur-Cantarini Fellowship program. F.D. and D.L. have received funding from Région Ile-de-France and Fondation pour la Recherche Médicale grants to support this study, We thank the members of the Cecere laboratory, D. Canzio, N. Iovino, R. Sawarkar and P. Andersen for discussions of the manuscript, the Miska, the Mello, the Kennedy, the Seydoux, the Claycomb, the Strome and the Dumont laboratories for sharing strains and/or antibodies. Some strains were provided by the CGC, funded by NIH Office of Research Infrastructure Programs (P40 OD010440)., and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Gene Editing, MESH: CRISPR-Cas Systems, Small RNA, MESH: Argonaute Proteins / deficiency, MESH: Caenorhabditis elegans Proteins / metabolism, Inheritance Patterns, MESH: RNA, Small Interfering / genetics, MESH: Argonaute Proteins / metabolism, medicine.disease_cause, MESH: RNA, Antisense / genetics, MESH: Argonaute Proteins / genetics, Animals, Genetically Modified, Histones, 0302 clinical medicine, MESH: Histones / metabolism, MESH: Animals, RNA, Small Interfering, MESH: Caenorhabditis elegans / genetics, Caenorhabditis elegans, Gene Editing, 0303 health sciences, Mutation, MESH: RNA, Messenger / metabolism, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Biological Evolution, Cell biology, Histone, MESH: Fertility / genetics, 030220 oncology & carcinogenesis, Argonaute Proteins, Piwi RNAs, MESH: RNA, Messenger / genetics, MESH: Gene Silencing, Epigenetic memory, endocrine system, MESH: Mutation, MESH: Caenorhabditis elegans / metabolism, Piwi-interacting RNA, MESH: Biological Evolution, Biology, Article, MESH: Animals, Genetically Modified, 03 medical and health sciences, medicine, Animals, Gene silencing, RNA, Antisense, Gene Silencing, RNA, Messenger, MESH: RNA, Antisense / metabolism, Caenorhabditis elegans Proteins, Gene, Repetitive Sequences, Nucleic Acid, 030304 developmental biology, MESH: RNA, Small Interfering / metabolism, MESH: Repetitive Sequences, Nucleic Acid, MESH: Histones / genetics, urogenital system, RNA, Cell Biology, biology.organism_classification, Fertility, RNAi, biology.protein, MESH: Caenorhabditis elegans Proteins / genetics, MESH: Inheritance Patterns, CRISPR-Cas Systems
Abstract

International audience; PIWI-interacting RNAs (piRNAs) promote fertility in many animals. However, whether this is due to their conserved role in repressing repetitive elements (REs) remains unclear. Here, we show that the progressive loss of fertility in Caenorhabditis elegans lacking piRNAs is not caused by derepression of REs or other piRNA targets but, rather, is mediated by epigenetic silencing of all of the replicative histone genes. In the absence of piRNAs, downstream components of the piRNA pathway relocalize from germ granules and piRNA targets to histone mRNAs to synthesize antisense small RNAs (sRNAs) and induce transgenerational silencing. Removal of the downstream components of the piRNA pathway restores histone mRNA expression and fertility in piRNA mutants, and the inheritance of histone sRNAs in wild-type worms adversely affects their fertility for multiple generations. We conclude that sRNA-mediated silencing of histone genes impairs the fertility of piRNA mutants and may serve to maintain piRNAs across evolution.

Published
2020

3. Endoplasmic reticulum stress controls iron metabolism through TMPRSS6 repression and hepcidin mRNA stabilization by RNA-binding protein HuR

Author

Belot, Audrey, Gourbeyre, Ophélie, Palin, Anais, Rubio, Aude, Largounez, Amélie, Besson-Fournier, Celine, Latour, Chloé, Lorgouilloux, Megane, Gallitz, Inka, Montagner, Alexandra, Polizzi, Arnaud, Régnier, Marion, Smati, Sarra, Zhang, An-Sheng, Diaz-Munoz, Manuel, Steinbicker, Andrea, Guillou, Hervé, Roth, Marie-Paule, Coppin, Hélène, Meynard, Delphine, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Oregon Health and Science University [Portland] (OHSU), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cooley's Anemia Foundation, French Foundation for Rare Diseases, German Research Foundation (DFG) : STE-1985/4-1, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA : R01DK102791, ATIP-AVENIR (INSERM/CNRS) program, Plan-Cancer : C18003BS, ANR-15-CE14-0026,Hepatokind,FGF21 contrôle homéostasie glucidique via les facteurs de transcription ChREBP et PPARa(2015), ANR-17-CE14-0036,IRONASH,Rôle du fer dans la pathologie du NASH(2017), ANR-17-CE14-0031,MTREAT-2,Manipuler la Matriptase-2 pour traiter les pathologies associées à une dérégulation du métabolisme du fer(2017), ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011), LESUR, Hélène, FGF21 contrôle homéostasie glucidique via les facteurs de transcription ChREBP et PPARa - - Hepatokind2015 - ANR-15-CE14-0026 - AAPG2015 - VALID, Rôle du fer dans la pathologie du NASH - - IRONASH2017 - ANR-17-CE14-0036 - AAPG2017 - VALID, Manipuler la Matriptase-2 pour traiter les pathologies associées à une dérégulation du métabolisme du fer - - MTREAT-22017 - ANR-17-CE14-0031 - AAPG2017 - VALID, Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID, and Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity)

Subjects
MESH: Humans, MESH: Membrane Proteins / genetics, Iron, Serine Endopeptidases, Membrane Proteins, RNA-Binding Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Endoplasmic Reticulum Stress, MESH: Serine Endopeptidases / genetics, MESH: Hepcidins* / metabolism, MESH: RNA-Binding Proteins, Hepcidins, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: RNA, Messenger / genetics, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, MESH: Endoplasmic Reticulum Stress* / genetics, MESH: Membrane Proteins / metabolism, RNA, Messenger, MESH: Hepcidins* / genetics, MESH: Iron / metabolism, Letters to the Editor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; The liver hormone hepcidin controls the main inflows of iron into plasma by binding to and inducing the degradation or the occlusion of the iron export activity of ferroportin, the only known cellular exporter of iron. When hepcidin concentrations are high, iron is trapped in enterocytes of the duodenum, hepatocytes, and macrophages. Hepcidin production by the hepatocytes is induced by a number of stimuli, most notably iron, through the BMP-SMAD signaling pathway, and inflammatory signals, through the IL-6/ STAT3 signaling axis. In addition, hepcidin has also been reported to respond to intracellular stress, namely endoplasmic reticulum (ER) stress which is involved in a number of pathophysiological states, including the inflammatory response, nutrient disorders and viral infection. A previous study has suggested that hepcidin induction by ER stress is controlled by the BMP-SMAD pathway,5 but the exact mechanism is still uncertain

Published
2021

4. Upregulation of Bone Morphogenetic Protein-1/Mammalian Tolloid and Procollagen C-Proteinase Enhancer-1 in Corneal Scarring

Author

Stéphane Galiacy, P. Fournié, Myriam Cassagne, François Malecaze, Dawiyat Massoudi, Catherine Moali, Marilyne Malbouyres, Cyrielle Tricoire, David J.S. Hulmes, Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Institut de Génomique Fonctionnelle de Lyon (IGFL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de Biologie Cellulaire et Cytologie, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CARBILLET, Véronique, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT), and École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
Male, collagen, Pathology, MESH: Corneal Injuries / metabolism, MESH: RNA, Messenger / biosynthesis, MESH: Extracellular Matrix Proteins / genetics, Bone Morphogenetic Protein 1, Cornea, Mice, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, PCPE1, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Up-Regulation, MESH: Animals, MESH: Aged, Extracellular Matrix Proteins, MESH: Middle Aged, MESH: Bone, Reverse Transcriptase Polymerase Chain Reaction, Proteolytic enzymes, MESH: Follow-Up Studies, Middle Aged, Immunohistochemistry, Sensory Systems, 3. Good health, Up-Regulation, MESH: Cornea / metabolism, MESH: Corneal Injuries / pathology, medicine.anatomical_structure, MESH: Glycoproteins / genetics, MESH: Young Adult, MESH: Bone Morphogenetic Protein 1 / genetics, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Microscopy, Electron, Transmission, MESH: RNA, Messenger / genetics, Female, MESH: Cornea / ultrastructure, Adult, medicine.medical_specialty, MESH: Morphogenetic Protein 1 / biosynthesis, BMP1, MESH: Extracellular Matrix Proteins / biosynthesis, Biology, MESH: Cicatrix / metabolism, MESH: Cicatrix / pathology, Bone morphogenetic protein 1, Cellular and Molecular Neuroscience, Cicatrix, Young Adult, MESH: Glycoproteins / biosynthesis, Stroma, Downregulation and upregulation, Microscopy, Electron, Transmission, medicine, Animals, Humans, RNA, Messenger, MESH: Mice, Corneal Scar, Aged, Glycoproteins, Wound Healing, MESH: Humans, corneal wound healing, MESH: Adult, MESH: Immunohistochemistry, Molecular biology, MESH: Male, Ophthalmology, Procollagen peptidase, Disease Models, Animal, MESH: Wound Healing, MESH: Cicatrix / genetics, MESH: Disease Models, Animal, Wound healing, MESH: Female, Corneal Injuries, Follow-Up Studies
Abstract

International audience; Purpose: To characterize the expression of the bone morphogenetic protein-1 (BMP-1)/tolloid-like proteinases (collectively called BTPs), which include BMP-1, mammalian tolloid (mTLD), and mammalian tolloid-like 1 (mTLL-1) and 2 (mTLL-2), as well as the associated proteins procollagen C-proteinase enhancers (PCPE-1 and -2), in corneal scarring. Methods: Using a mouse full-thickness corneal excision model, wound healing was followed for up to 28 days by transmission electron microscopy, immunohistology (BMP-1/mTLD and PCPE-1), and quantitative PCR (Q-PCR: collagen III, BMP-1/mTLD, mTLL-1, mTLL-2, PCPE-1, PCPE-2). Bone morphogenetic protein-1/mTLD and PCPE-1 were also immunolocalized in cases of human corneal scarring following injuries. Results: In the mouse model, throughout the follow-up period, there was a large increase in collagen III mRNA expression in the stroma. By transmission electron microscopy, there was marked cellular infiltration into the wound as well as disorganization of collagen fibrils, but no significant difference in fibril diameter. In control corneas, by Q-PCR, BMP-1/mTLD showed the highest expression, compared to low levels of mTLL-1 and undetectable levels of mTLL-2, in both epithelium and stroma. Following wounding, both BMP-1/mTLD and PCPE-1 mRNA and protein increased, while PCPE-2 mRNA decreased. Finally, by immunofluorescence, BMP-1/mTLD and PCPE-1 were strongly expressed in the scar region in both mouse and human corneas. Conclusions: Bone morphogenetic protein-1/mTLD and PCPE-1 are upregulated in corneal scars. Both proteins may therefore contribute to the process of corneal scarring.

Published
2014

5. Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in treated HIV-infected individuals

Author

Fatima-Ezzahra L’Faqihi, Pierre Delobel, Jacques Izopet, Christophe Pasquier, Mary Requena, Jacques Amar, Martine Dubois, Patrice Massip, Maud Mavigner, Bruno Marchou, Pascale Klopp, Karl Barange, Laurent Alric, Michelle Cazabat, Jean-Pierre Vinel, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], GeT-Sante, Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Polarisation des Macrophages et Récepteurs Nucléaires dans les Pathologies Inflammatoires et Infectieuses, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR50, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Pagès, Nathalie

Subjects
MESH: CD4-Positive T-Lymphocytes / immunology, CD4-Positive T-Lymphocytes, Integrin beta Chains, [SDV]Life Sciences [q-bio], MESH: Cell Movement / immunology, HIV Infections, Systemic inflammation, MESH: Antiretroviral Therapy, Highly Active, MESH: Integrin beta Chains / metabolism, MESH: Th17 Cells / immunology, MESH: HIV-1, Intestinal mucosa, Cell Movement, T-Lymphocyte Subsets, Antiretroviral Therapy, Highly Active, Intestine, Small, Intestinal Mucosa, education.field_of_study, MESH: Immunity, Mucosal / drug effects, MESH: RNA, Messenger / metabolism, MESH: Intestine, Small / immunology, General Medicine, MESH: Case-Control Studies, MESH: T-Lymphocyte Subsets / pathology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Chemokines, CC, MESH: T-Lymphocyte Subsets / immunology, MESH: RNA, Messenger / genetics, medicine.symptom, MESH: Receptors, CCR / metabolism, Research Article, MESH: Chemokines, CC / metabolism, T cell, Population, MESH: HIV Infections / drug therapy, MESH: Chemokines, CC / genetics, Biology, MESH: HIV Infections / pathology, Receptors, CCR, Immune system, MESH: HIV Infections / genetics, medicine, Humans, MESH: Intestinal Mucosa / immunology, RNA, Messenger, education, Immunity, Mucosal, MESH: Humans, MESH: Th17 Cells / pathology, MESH: Intestine, Small / pathology, MESH: CD4-Positive T-Lymphocytes / pathology, Gut-specific homing, Small intestine, Case-Control Studies, Immunology, HIV-1, Th17 Cells, Homing (hematopoietic), MESH: Intestinal Mucosa / pathology, MESH: HIV Infections / immunology
Abstract

International audience; Depletion of CD4+ T cells from the gut occurs rapidly during acute HIV-1 infection. This has been linked to systemic inflammation and disease progression as a result of translocation of microbial products from the gut lumen into the bloodstream. Combined antiretroviral therapy (cART) substantially restores CD4+ T cell numbers in peripheral blood, but the gut compartment remains largely depleted of such cells for poorly understood reasons. Here, we show that a lack of recruitment of CD4+ T cells to the gut could be involved in the incomplete mucosal immune reconstitution of cART-treated HIV-infected individuals. We investigated the trafficking of CD4+ T cells expressing the gut-homing receptors CCR9 and integrin α4β7 and found that many of these T cells remained in the circulation rather than repopulating the mucosa of the small intestine. This is likely because expression of the CCR9 ligand CCL25 was lower in the small intestine of HIV-infected individuals. The defective gut homing of CCR9+β7+ CD4+ T cells - a population that we found included most gut-homing Th17 cells, which have a critical role in mucosal immune defense - correlated with high plasma concentrations of markers of mucosal damage, microbial translocation, and systemic T cell activation. Our results thus describe alterations in CD4+ T cell homing to the gut that could prevent efficient mucosal immune reconstitution in HIV-infected individuals despite effective cART.

Published
2011

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