Wound healing across the animal kingdom: Crosstalk between the immune system and the extracellular matrix

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Arenas Gómez, Claudia M., Sabin, K. Z., & Echeverri, K. Wound healing across the animal kingdom: Crosstalk between the immune system and the extracellular matrix. Developmental Dynamics, (2020): 1-13, doi:10.1002/dvdy.178.Tissue regeneration is widespread in the animal kingdom. To date, key roles for different molecular and cellular programs in regeneration have been described, but the ultimate blueprint for this talent remains elusive. In animals capable of tissue regeneration, one of the most crucial stages is wound healing, whose main goal is to close the wound and prevent infection. In this stage, it is necessary to avoid scar formation to facilitate the activation of the immune system and remodeling of the extracellular matrix, key factors in promoting tissue regeneration. In this review, we will discuss the current state of knowledge regarding the role of the immune system and the interplay with the extracellular matrix to trigger a regenerative response.The research in the Echeverri lab is supported NIH NCID R01 to Karen Echeverri and start‐up funds from the MBL. Keith Z. Sabin has been supported by an NIH T32 GM113846 grant

AP-1cFos/JunB/miR-200a regulate the pro-regenerative glial cell response during axolotl spinal cord regeneration

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Sabin, Keith Z., Jiang, Peng, Gearhart, Micah D., Stewart, Ron, & Echeverri, Karen. AP-1cFos/JunB/miR-200a regulate the pro-regenerative glial cell response during axolotl spinal cord regeneration. Communications Biology, 2(91), (2019), doi:10.1038/s42003-019-0335-4.Salamanders have the remarkable ability to functionally regenerate after spinal cord transection. In response to injury, GFAP+ glial cells in the axolotl spinal cord proliferate and migrate to replace the missing neural tube and create a permissive environment for axon regeneration. Molecular pathways that regulate the pro-regenerative axolotl glial cell response are poorly understood. Here we show axolotl glial cells up-regulate AP-1cFos/JunB after injury, which promotes a pro-regenerative glial cell response. Injury induced upregulation of miR-200a in glial cells supresses c-Jun expression in these cells. Inhibition of miR-200a during regeneration causes defects in axonal regrowth and transcriptomic analysis revealed that miR-200a inhibition leads to differential regulation of genes involved with reactive gliosis, the glial scar, extracellular matrix remodeling and axon guidance. This work identifies a unique role for miR-200a in inhibiting reactive gliosis in axolotl glial cells during spinal cord regeneration.This reseach was supported by a Regenerative Medicine Minnesota Grant and a NIH NCID R01 to KE. KZS has been supported by a NIH T32 GM113846 grant

Approaches to Improve the Surveillance, Monitoring, and Management of Noncommunicable Diseases in HIV-Infected Persons: Viewpoint.

Low-income and middle-income countries (LMICs) are undergoing an epidemiological transition, in which the burden of noncommunicable diseases (NCDs) is rising and mortality will shift from infectious diseases to NCDs. Specifically, cardiovascular disease, diabetes, renal diseases, chronic respiratory diseases, and cancer are becoming more prevalent. In some regions, particularly sub-Saharan Africa, the dual HIV and NCD epidemics will pose challenges because their joint burden will have adverse effects on the quality of life and will likely increase global inequities. Given the austere clinical infrastructure in many LMICs, innovative models of care delivery are needed to provide comprehensive care in resource-limited settings. Improved data collection and surveillance of NCDs among HIV-infected persons in LMICs are necessary to inform integrated NCD-HIV prevention, care, and treatment models that are effective across a range of geographic settings. These efforts will preserve the considerable investments that have been made to prevent the number of lives lost to HIV, promote healthy aging of persons living with HIV, and contribute to meeting United Nations Sustainable Development Goals

\u3ci\u3e Glioblastoma Derived Exosomes Induce Apoptosis in Cytotoxic T Cells Through a Fas Ligand Mediated Mechanism \u3c/i\u3e

INTRODUCTION: Glioblastoma multiforme deploy s a number of weapons to thwart the immune system. Within the tumor microenvironment, cytotoxic T cells fall victim to Fas ligand (FasL) induced apoptosis. In prostate and colorectal cancer, exosomes can mediate this FasL induced T cell apoptosis. Exosomes are tiny, membrane bound vesicles that are released from a cell. They contain functional mRNA and protein and have cell surface molecules representative of their parent cell. It is not known if GBM derived exosomes can also mediate FasL triggered apoptosis. In this study, the role of tumor derived exosomes as the delivery vehicle for FasL is explored. METHODS: Exosomes are isolated from the T98 cell line using differential ultracentrifugation. FasL expression in the cell line and derived exosomes is determined using reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. GBM derived exosomes, recombinant FasL, and exosomes treated with an anti-FasL antibody are co-cultured with Jurkat A3 T cells. Apoptosis is measured using a caspase-8 luminescent assay. RESULTS: FasL is expressed by the T98 cell line and is present on the surface of the cells and their exosomes (Figure 1). Caspase-8 activation is seen in T cells treated with GBM derived exosomes and recombinant FasL, but not with exosomes treated with anti-FasL antibody or exosome free supernatant (Figure 2). CONCLUSION: GBM derived exosomes induce T cell apoptosis through a FasL mediated mechanism. This method of immune suppression has not previously been described. This research opens new avenues to antagonize GBM related immune system malfunction

\u3ci\u3e Glioblastoma derived exosomes contribute to tumor immune evasion \u3c/i\u3e

Glioblastoma multiforme (GBM) is the most frequent and lethal primary brain tumor in adults. Despite intense biomedical research, the median survival after diagnosis is 15 months. One factor contributing to this poor prognosis is the immune protection afforded by the tumor microenvironment. Tumors have a diverse repertoire of immune-evasive techniques. One method of evasion not well explored is the release of tumor-derived exosomes. Exosomes are tiny membrane-bound vesicles of endocytic origin that contain viable mRNA and functional proteins that can affect the physiology of recipient cells. Exosome release has been reported for numerous cancer types, including GBM. Exosomes from colon cancer have been shown to carry Fas ligand (FasL) and to induce apoptosis of activated T cells. The aim of this study was to elucidate whether the same immune-evasive technique is used in GBM. GBM exosomes were isolated from the serum-free culture medium of U87 MG and U138 MG cells by using differential ultracentrifugation and were then resuspended in phosphate-buffered saline. The protein concentration of the resulting exosome pellet was determined, and subsequent exosome treatments were based on protein concentration. A3T T cells were plated at a concentration of 10,000 cells per well in 96-well plates and were treated with quantified exosome fractions or with recombinant FasL, and T cell proliferation was determined. Our data demonstrated that tumor-derived exosomes significantly inhibited the proliferation of T cells and that the cellular inhibition resulting from the exosomes was comparable to that seen with the recombinant FasL. These results suggest that targeting FasL in GBM could greatly decrease the amount of immune suppression that occurs at the tumor site

Opportunities for Enhanced Strategic Use of Surveys, Medical Records, and Program Data for HIV Surveillance of Key Populations: Scoping Review.

BACKGROUND: Normative guidelines from the World Health Organization recommend tracking strategic information indicators among key populations. Monitoring progress in the global response to the HIV epidemic uses indicators put forward by the Joint United Nations Programme on HIV/AIDS. These include the 90-90-90 targets that require a realignment of surveillance data, routinely collected program data, and medical record data, which historically have developed separately. OBJECTIVE: The aim of this study was to describe current challenges for monitoring HIV-related strategic information indicators among key populations ((men who have sex with men [MSM], people in prisons and other closed settings, people who inject drugs, sex workers, and transgender people) and identify future opportunities to enhance the use of surveillance data, programmatic data, and medical record data to describe the HIV epidemic among key populations and measure the coverage of HIV prevention, care, and treatment programs. METHODS: To provide a historical perspective, we completed a scoping review of the expansion of HIV surveillance among key populations over the past three decades. To describe current efforts, we conducted a review of the literature to identify published examples of SI indicator estimates among key populations. To describe anticipated challenges and future opportunities to improve measurement of strategic information indicators, particularly from routine program and health data, we consulted participants of the Third Global HIV Surveillance Meeting in Bangkok, where the 2015 World Health Organization strategic information guidelines were launched. RESULTS: There remains suboptimal alignment of surveillance and programmatic data, as well as routinely collected medical records to facilitate the reporting of the 90-90-90 indicators for HIV among key populations. Studies (n=3) with estimates of all three 90-90-90 indicators rely on cross-sectional survey data. Programmatic data and medical record data continue to be insufficiently robust to provide estimates of the 90-90-90 targets for key populations. CONCLUSIONS: Current reliance on more active data collection processes, including key population-specific surveys, remains warranted until the quality and validity of passively collected routine program and medical record data for key populations is optimized

Know Your Epidemic, Strengthen Your Response: Developing a New HIV Surveillance Architecture to Guide HIV Resource Allocation and Target Decisions

To guide HIV prevention and treatment activities up to 2020, we need to generate and make better use of high quality HIV surveillance data. To highlight our surveillance needs, a special collection of papers in JMIR Public Health and Surveillance has been released under the title "Improving Global and National Responses to the HIV Epidemic Through High Quality HIV Surveillance Data." We provide a summary of these papers and highlight methods for developing a new HIV surveillance architecture