106 research outputs found
Reduced Il17a expression distinguishes a Ly6c lo MHCIIhi macrophage population promoting wound healing
No full textMacrophages are the main components of inflammation during skin wound healing. They are critical in wound closure and in excessive inflammation, resulting in defective healing observed in chronic wounds. Given the heterogeneity of macrophage phenotypes and functions, we here hypothesized that different subpopulations of macrophages would have different and sometimes opposing effects on wound healing. Using multimarker flow cytometry and RNA expression array analyses on macrophage subpopulations from wound granulation tissue, we identified a Ly6c lo MHCIIhi "noninflammatory" subset that increased both in absolute number and proportion during normal wound healing and was missing in Ob/Ob and MYD88-/-models of delayed healing. We also identified IL17 as the main cytokine distinguishing this population from proinflammatory macrophages and demonstrated that inhibition of IL17 by blocking Ab or in IL17A-/-mice accelerated normal and delayed healing. These findings dissect the complexity of the role and activity of the macrophages during wound inflammation and may contribute to the development of therapeutic approaches to restore healing in chronic wounds
Type I interferonâ-mediated monogenic autoinflammation:The type i interferonopathies, a conceptual overview
No full textType I interferon is a potent substance. As such, the induction, transmission, and resolution of the type I interferonâ-mediated immune response are tightly regulated. As defined, the type I interferonopathies represent discrete examples of a disturbance of the homeostatic control of this system caused by Mendelian mutations. Considering the complexity of the interferon response, the identification of further monogenic diseases belonging to this disease grouping seems likely, with the recognition of type I interferonopathies becoming of increasing clinical importance as treatment options are developed based on an understanding of disease pathology and innate immune signaling. Definition of the type I interferonopathies indicates that autoinflammation can be both interferon and noninterferon related, and that a primary disturbance of the innate immune system can spill over into autoimmunity in some cases. Indeed, that several non-Mendelian disorders, most particularly systemic lupus erythematosus and dermatomyositis, are also characterized by an up-regulation of type I interferon signaling suggests the possibility that insights derived from this work will have relevance to a broader field of clinical medicine.</p
Interleukin-23 regulates interleukin-17 expression in wounds, and its inhibition accelerates diabetic wound healing through the alteration of macrophage polarization
No full textInflammation is a critical phase in the healing of skin wounds. Excessive inflammation and inflammatory macrophages are known to cause impaired wound closure and outcome. This prompted us to test the role of IL-23 in IL-17 expression and in modulating wound inflammation and macrophage polarization. Full-thickness wounds (4 × 6 mm) were created on the dorsal surface of multiple genetically modified mouse models. Obese diabetic mouse wounds were treated with anti-IL-17A, anti-IL-23, or isotype-matched antibodies. We found IL-23- but not IL-12-deficient mice displayed significantly reduced IL-17 expression in wounds. This was rescued by delivery of recombinant IL-23. IL-23- and IL-17-deficient mice showed a significant increase in noninflammatory macrophages. Obese diabetic mice treated with anti-IL-17A and anti-IL-23p19 blocking antibodies had significantly improved wound reepithelialization. Similarly, IL-17-/- obese mice had accelerated wound closure, resulting in reduced iNOS expression and inflammatory macrophages while maintaining prohealing CD206 and lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1)-expressing macrophages. This study highlights the importance of the IL-17 pathway in wound closure offering new possibilities of therapeutic intervention in chronic wounds.-Lee, J., Rodero, M. P., Patel, J., Moi, D., Mazzieri, R., Khosrotehrani, K. Interleukin-23 regulates interleukin-17 expression in wounds, and its inhibition accelerates diabetic wound healing through the alteration of macrophage polarization
Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome
No full textShiga toxin (Stx)producing Escherichia coli is the main etiological agent that causes hemolytic uremic syndrome (HUS), a microangiopathic disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Although direct cytotoxic effects on endothelial cells by Stx are the primary pathogenic event, there is evidence that indicates the inflammatory response mediated by polymorphonuclear neutrophils and monocytes as the key event during HUS development. Because the chemokine receptor CCR1 participates in the pathogenesis of several renal diseases by orchestrating myeloid cell kidney infiltration, we specifically addressed the contribution of CCR1 in a murine model of HUS. We showed that Stx type 2treated CCR1 -/- mice have an increased survival rate associated with less functional and histological renal damage compared with control mice. Stx type 2triggered neutrophilia and monocytosis and polymorphonuclear neutrophil and monocyte renal infiltration were significantly reduced and delayed in CCR1 -/- mice compared with control mice. In addition, the increase of the inflammatory cytokines (tumor necrosis factor-α and IL-6) in plasma was delayed in CCR1 -/- mice compared with control mice. These data demonstrate that CCR1 participates in cell recruitment to the kidney and amplification of the inflammatory response that contributes to HUS development. Blockade of CCR1 could be important to the design of future therapies to restrain the inflammatory response involved in the development of HUS.Fil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Auvynet, Constance. Universite Pierre et Marie Curie; Francia. Inserm; FranciaFil: Poupel, Lucie. Inserm; Francia. Universite Pierre et Marie Curie; FranciaFil: Rodero, Mathieu. Universite Pierre et Marie Curie; Francia. Inserm; FranciaFil: Mejias, María Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Panek, Cecilia Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Combadiere, Christophe. Universite Pierre et Marie Curie; Francia. Inserm; FranciaFil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin
On the use of Biplot analysis for multivariate bibliometric and scientific indicators
No full textBibliometric mapping and visualization techniques represent one of the main pillars in the field of scientometrics. Traditionally, the main methodologies employed for representing data are Multi-Dimensional Scaling, Principal Component Analysis or Correspondence Analysis. In this paper we aim at presenting a visualization methodology known as Biplot analysis for representing bibliometric and science and technology indicators. A Biplot is a graphical representation of multivariate data, where the elements of a data matrix are represented according to dots and vectors associated with the rows and columns of the matrix. In this paper we explore the possibilities of applying the Biplot analysis in the research policy area. More specifically we will first describe and introduce the reader to this methodology and secondly, we will analyze its strengths and weaknesses through three different study cases: countries, universities and scientific fields. For this, we use a Biplot analysis known as JK-Biplot. Finally we compare the Biplot representation with other multivariate analysis techniques. We conclude that Biplot analysis could be a useful technique in scientometrics when studying multivariate data and an easy-to-read tool for research decision makers
Biallelic mutations in MTPAP associated with a lethal encephalopathy
No full textBackground A homozygous founder mutation in MTPAP/TENT6, encoding mitochondrial
poly(A) polymerase (MTPAP), was first reported in six individuals of Old Order
Amish descent demonstrating an early-onset, progressive spastic ataxia with optic
atrophy and learning difficulties. MTPAP contributes to the regulation ofmitochondrial
gene expression through the polyadenylation of mitochondrially encoded mRNAs.
Mitochondrial mRNAs with severely truncated poly(A) tails were observed in affected
individuals, and mitochondrial protein expression was altered.
Objective To determine the genetic basis of a perinatal encephalopathy associated with
stereotyped neuroimagingandinfantile death in three patients fromtwounrelated families.
Methods Whole-exome sequencing was performed in two unrelated patients and the
unaffected parents of one of these individuals. Variants and familial segregation were
confirmed by Sanger sequencing. Polyadenylation of mitochondrial transcripts and de
novo synthesis of mitochondrial proteins were assessed in patient’s fibroblasts
Wound-associated macrophages control collagen 1α2 transcription during the early stages of skin wound healing.
No full textWound-associated fibrosis is important to provide tensile strength upon wound healing but at the same time is detrimental to proper tissue regeneration. To date, there is no clear evidence of the role of macrophages and their subpopulations in the control of the kinetics of collagen production during wound healing. To evaluate in vivo the contribution of macrophages in collagen transcription, we depleted macrophages after wounding luciferase reporter mice of the collagen 1 alpha 2 (Col 1α2) promoter activity. Our data reveal that Col 1α2 starts to be transcribed at D2 after wounding, reaching a plateau after 7 days. Sustained macrophage depletion significantly reduced collagen 1α2 transcription from D4, indicating that the control of fibrosis by macrophages occurs during the early stages of the wound healing process. In conclusion, our results demonstrate an important role of wound macrophages in the control of collagen production during wound healing
- …
