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Frontiers of Medicine 2022年第6期16卷 827-858页

作者： Kosar Babaei Mohsen Aziminezhad Seyedeh Elham Norollahi Sogand Vahidi Ali Akbar Samadani Non-Communicable Disease Research Center Neyshabur University of Medical SciencesNeyshaburIran UMR INSERM U 1122 IGE-PCVInteractions Gène-Environment En Physiopathologie Cardiovascular UniversitéDe LorraineNancyFrance Cancer Research Center and Department of Immunology Semnan University of Medical SciencesSemnanIran Medical Biology Research Center Kermanshah University of Medical SciencesKermanshahIran Guilan Road Trauma Research Center Guilan University of Medical SciencesRashtIran

Infertility is experienced by 8%–12%of adults in their reproductive period globally and has become a prevalent concern.Besides routine therapeutic methods,stem cells are rapidly being examined as viable alternative therapies in regenerative medicine and translational investigation.Remarkable progress has been made in understanding the biology and purpose of stem cells.The affected pluripotent stem cells(iPSCs)and mesenchymal stem cells(MSCs)are further studied for their possible use in reproductive medicine,particularly for infertility induced by premature ovarian insufficiency and azoospermia.Accordingly,this study discusses current developments in the use of some kinds of MSCs such as adipose-derived stem cells,bone marrow stromal cells,umbilical cord MSCs,and menstrual blood MSCs.These methods have been used to manage ovarian and uterine disorders,and each technique presents a novel method for the therapy of infertility.

关键词： infertility stem cell therapy mesenchymal stem cells pluripotent stem cells

Mediator contributes to IgH locus VDJ rearrangements by promoting usage of most distal V segments

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Cellular & Molecular Immunology 2020年第4期17卷 407-409页

作者： Iman Dalloul Zeinab Dalloul Sandrine Le Noir François Boyer Bernardo Reina-San-Martin Jeanne Cook-Moreau Michel Cogné umr CNRS 7276 INSERM U1262Universite de LimogesLimoges 87025France inserm u1258 UMR CNRS 7104Institut de Genetique et de Biologie Moleculaire et CellulaireUniversitéde StrasbourgIllkirch 67400France

INTRODuCTION The immunoglobulin heavy(IgH)chain locus includes a large cluster of V,D and J segments spanning thousands of kilobases in mammals and its expression implies long-range 3D-regulation of various gene modifications.1 V(D)J recombination occurs during early B-cell ontogeny.2 It is regulated by multiple transcription factors and cis-regulatory elements,and most notably by the intronic 5′Eμelement located in the JH to Cμintron.3 The intergenic control region 1(IGCR1)located between the VH and D gene clusters inhibits rearrangement of the most DH-proximal VH gene segments,while promoting usage of distal VH gene segments.4 Other downstream elements of the locus,flanking its 3′end might have more subtle roles:while the large 3′regulatory region(3′RR)shows strong internal synergies2 and behaves as a superenhancer in mature B cells.Its deletion showed no influence on the VDJ repertoire and rather increased transcription of unrearranged V segments.3–5 Insulators binding CTCF farther downstream of the 3′RR were shown,however,to promote usage of distal VH segments.6 Altogether,there are strong indications that elements involved in long-distance regulation of transcription might also influence VDJ recombination.In-frame splicing of VDJ exons is also needed for full Ig expression.7 Given the functional importance of gene architecture and long-range interactions for the IgH locus physiology,we explored the dependence of the VDJ repertoire on Med1,a known actor of long-range enhancer interactions.

关键词： B cells mediator VDJ repertoire

Autophagy in dendritic cells

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Cellular & Molecular Immunology 2018年第11期15卷 944-952页

作者： Ghita Ghislat Toby Lawrence Centre d‘Immunologie de Marseille-Luminy InsermU1104CNRS UMR7280MarseilleFrance

Autophagy and immunity share the property of being auto-protective for the organism.Autophagy is an important degradation pathway that buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man.Perturbations in autophagy are associated with inflammation and cancer development.Emerging studies have characterized the molecular details regarding how autophagy is controlled by immune cells.Among these,dendritic cells(DCs)are one of the most potent professional antigen-presenting cells critical for the activation of naïve T cells to maintain immune tolerance and drive protective immunity to infection and cancer.DCs undergo functional maturation that can either lead to an immunostimulatory phenotype,as in the context of infection,or to a tolerogenic phenotype associated with immunosuppression to self-antigens,as well as to cancer.An increasing number of recent studies has characterized the involvement of autophagy in DC functions in various physiological and pathological contexts.Here,we provide a comprehensive review of these outcomes and discuss the limitation of the models used and the forefront of the knowledge concerning the crosstalk between autophagy and DC biology.

关键词： autophagy dendritic cells maturation

Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases

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Neural Regeneration Research 2017年第9期12卷 1418-1421页

作者： Laura Foucault-Fruchard Daniel Antier umr inserm u930 Université Fran?ois Rabelais CHRu de Tours H?pital Bretonneau

Neurodegenerative diseases, such as Alzheimer＇s, Parkinson＇s and Huntington＇s diseases, are all character- ized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated in vivo and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist.

关键词： α7 nicotinic receptors cholinergic anti-inflammatory pathway Alzheimer＇s disease Huntington＇s disease Parkinson＇s disease neuroinflammation neurodegeneration positive allosteric modulators

OTX2 stimulates adult retinal ganglion cell regeneration

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Neural Regeneration Research 2022年第3期17卷 690-696页

作者： Raoul Torero Ibad Nicole Quenech’du Alain Prochiantz Kenneth L.Moya Centre for Interdisciplinary Research in Biology(CIRB) Collége de FranceCNRS UMR 7241INSERM U1050Labex MemoLifeParis Sciences et Lettres Research UniversityParisFrance

Retinal ganglion cell(RGC) axons provide the only link between the light sensitive and photon transducing neural retina and visual centers of the brain.RGC axon degeneration occurs in a number of blinding diseases and the ability to stimulate axon regeneration from surviving ganglion cells could provide the anatomic substrate for restoration of vision.OTX2 is a homeoprotein transcription factor expressed in the retina and previous studies showed that,in response to stress,exogenous OTX2 increases the in vitro and in vivo survival of RGCs.Here we examined and quantified the effects of OTX2 on adult RGC axon regeneration in vitro and in vivo.The results show that exogenous OTX2 stimulates the regrowth of axons from RGCs in cultures of dissociated adult retinal cells and from explants of adult retinal tissue and that RGCs respond directly to OTX2 as regrowth is observed in cultures of purified adult rat RGCs.Importantly,after nerve crush in vivo,we observed a positive effect of OTX2 on the number of regenerating axons up to the optic chiasm within 14 days post crush and a very modest level of acuity absent in control mice.The effect of OTX2 on RGC survival and regeneration is of potential interest for degenerative diseases affecting this cell type.All animal procedures were approved by the local "Comié d'éιthique en expérimentation animale n°59" and authorization n° 00702.01 delivered March 28,2014 by the French "Ministére de l'enseignement supérieur et de la recherche".

关键词： axon regeneration dissociated retinal culture GAP-43 homeoprotein optic nerve crush OTX2 retinal explants retinal ganglion cell

Recombination-Independent Mechanisms and Pairing of Homologous Chromosomes during Meiosis in Plants

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Molecular Plant 2014年第3期7卷 492-501页

作者： Olivier Da Ines Maria E. Gallego Charles I. White Genetique Reproduction et Developpement UMR CNRS 6293 Clermont UniversitY INSERM U1103 63171 Aubiere France

Meiosis is the specialized eukaryotic cell division that permits the halving of ploidy necessary for game- togenesis in sexually reproducing organisms, This involves a single round of DNA replication followed by two successive divisions. To ensure balanced segregation, homologous chromosome pairs must migrate to opposite poles at the first meiotic division and this means that they must recognize and pair with each other beforehand. Although understanding of the mechanisms by which meiotic chromosomes find and pair with their homologs has greatly advanced, it remains far from being fully understood. With some notable exceptions such as male Drosophila, the recognition and physical link- age of homologs at the first meiotic division involves homologous recombination. However, in addition to this, it is clear that many organisms, including plants, have also evolved a series of recombination-independent mechanisms to facili- tate homolog recognition and pairing. These implicate chromosome structure and dynamics, telomeres, centromeres, and, most recently, small RNAs. With a particular focus on plants, we present here an overview of understanding of these early, recombination-independent events that act in the pairing of homologous chromosomes during the first meiotic division,

关键词： meiosis homolog pairing chromatin centromeres telomeres.

The epididymal immune balance:a key to preserving male fertility

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Asian Journal of Andrology 2019年第6期21卷 531-539页

作者： Allison Voisin Fabrice Saez Joel R Drevet Rachel Guiton Team Mechanisms of Posttesticular Infertility GReD LaboratoryCNRS UMR 6293-INSERM U1103 university of Clermont Auvergne Clermont-Ferrand 63001France

up to 15%of male in fertility has an immuno logical origi n,either due to repetitive infections or to autoimmune resp on ses mainly affecting the epididymis,prostate,and testis.Clinical observations and epidemiological data clearly contradict the idea that the testis confers immune protection to the whole male genital tract.As a consequenee,the epididymis,in which posttesticular spermatozoa mature and are stored,has raised some in terest in recent years when it comes to its immune mecha nisms.In deed,sperm cells are produced at puberty,long after the establishment of self-toleranee,and they possess unique surface proteins that cannot be recognized as self.These are potential targets of the immune system,with the risk of inducing autoantibodies and consequently male infertility.Epididymal immunity is based on a finely tuned equilibrium between efficient immune responses to pathogens and strong tolerance to sperm cells.These processes rely on incompletely described molecules and cell types.This review compiles recent studies focusing on the immune cell types populating the epididymis,and proposes hypothetical models of the organization of epididymal immunity with a special emphasis on the immune response,while also discussing important aspects of the epididymal immune regulation such as tolerance and tumour control.

关键词： epididymis immune response lymphocytes mononuclear phagocytes toleranee

Targeted therapies in breast cancer:New challenges to fight against resistance

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World Journal of Clinical Oncology 2017年第2期8卷 120-134页

作者： Viviana Masoud Gilles Pagès university Nice Sophia Antipolis Institute for Research on Cancer and Aging of Nice CNRS UMR7284/INSERM U 1081

Breast cancer is the most common type of cancer found in women and today represents a significant challenge to public health. With the latest breakthroughs in molecular biology and immunotherapy, very specific targeted therapies have been tailored to the specific pathophysiology of different types of breast cancers. These recent developments have contributed to a more efficient and specific treatment protocol in breast cancer patients. However, the main challenge to be further investigated still remains the emergence of therapeutic resistance mechanisms, which develop soon after the onset of therapy and need urgent attention and further elucidation. What are the recent emerging molecular resistance mechanisms in breast cancer targeted therapy and what are the best strategies to apply in order to circumvent this important obstacle? The main scope of this review is to provide a thorough update of recent developments in the field and discuss future prospects for preventing resistance mechanisms in the quest to increase overall survival of patients suffering from the disease.

关键词： Breast cancers Resistance Human epidermal growth factor receptor 2 Angiogenesis Triple negative Immune tolerance

The IgH 3′ regulatory region super-enhancer does not control IgA class switch recombination in the B1 lineage

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Cellular & Molecular Immunology 2018年第3期15卷 289-291页

作者： Hussein Issaoui Nour Ghazzaui Alexis Saintamand Claire Carrion Christelle Oblet Yves Denizot CNRS umr 7276 CRIBLUniversitéde LimogesLimogesFrance inserm u1236 UniversitéRennes 1RennesFrance

The bone marrow-derived B2 population represents the vast majority of bone marrow,blood,lymph node and splenic B-cells.Mouse B1 B-cells mostly originate during embryonic life in the liver and represent the main B-cell population in the pleural and peritoneal cavities.1,2,3,4,5 B1 and B2 B-cells differ in their origin,antigen specificity,cell surface markers,tissue distribution and capacity for class switch recombination(CSR).Schematically,B1 B-cells appear earlier than B2 B-cells during fetal development and maintain their self-renewal ability throughout their life.

关键词： maintain specificity mostly

Molecular analysis of γ1, γ3, and α class switch recombination junctions in APOBEC3-deficient mice using high-throughput sequencing

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Cellular & Molecular Immunology 2020年第4期17卷 418-420页

作者： Hussein Issaoui Mélissa Ferrad Nour Ghazzaui Sandrine Lecardeur Jeanne Cook-Moreau François Boyer Yves Denizot umr CNRS 7276 INSERM U1262Equipe Labellisée LIGUE 2018University of LimogesCBRSrue Pr.Descottes87025 LimogesFrance

Activation-induced deaminase(AID)is required for immunoglobulin(Ig)class switch recombination(CSR),in which the constant(C)μgene of IgM is substituted with C_(γ),C_(ε),or C_(α),thereby generating IgG,IgE,and IgA antibodies,respectively,with new effector functions but the same antigenic specificity.1 AID targets specific DNA switch(S)regions preceding C regions except for Cδ.2 Sμis usually the donor region,while Sγ,ε,αare the acceptor regions.AID deaminates C into u on single-stranded DNA by targeting the WRCY(W=A/T,R=A/G,and Y=C/T)hot motif and,to a lesser extent,the SYC(S=G/C,Y=C/T)cold motif.3,4 AID is a member of the apolipoprotein B editing complex(APOBEC)family.Among APOBEC genes,a family of evolutionarily conserved cytidine deaminases,APOBEC3 is implicated in diverse cell functions including innate immunity against retroviruses.4 The DNA-editing APOBEC3 enzymes have recently attracted attention due to their involvement in cancer and potential applications in gene editing.5–7 While a single copy of each APOBEC3 gene is present in rodents,seven copies of each APOBEC3 gene are found in humans.

关键词： immunity involvement thereby