{"id":618,"date":"2020-04-27T14:56:22","date_gmt":"2020-04-27T12:56:22","guid":{"rendered":"https:\/\/inspire.chu-toulouse.fr\/?page_id=618"},"modified":"2020-05-27T12:52:36","modified_gmt":"2020-05-27T10:52:36","slug":"immunity-and-inflammation","status":"publish","type":"page","link":"https:\/\/ihuhealthage.fr\/fr\/immunity-and-inflammation\/","title":{"rendered":"Immunity and inflammation"},"content":{"rendered":"<h2 class=\"chapeau\">The projects aim to \u00a0better characterize at the cellular and molecular levels the correlates of immune-senescence and inflammaging; \u00a0to pinpoint the pathways associated with specific immune alterations during biological aging.<\/h2>\n<h2><b>Identification of a specific monocyte signature to predict macrophage pro-inflammatory \/ pro-resolutive status during frailty phenotype<\/b><\/h2>\n<p><img loading=\"lazy\" decoding=\"async\" class=\" wp-image-1078 alignleft\" src=\"https:\/\/ihuhealthage.fr\/wp-content\/uploads\/2020\/05\/unnamed-2.png\" alt=\"\" width=\"142\" height=\"71\" \/>Inflammaging corresponds to a gradually augmenting inflammatory state associated with increased myelopoiesis in the bone marrow. This process increases the generation of mature and immature myeloid cells. Furthermore, aging is associated with delayed resolution of inflammation, reduced pro-resolving lipid mediators, and altered macrophage function. We hypothesized that the defect in pro-resolutive macrophages during aging depends on the modification of their differentiation and\/or activation.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p><span class=\"Apple-converted-space\">Principal investigators of this study:<br \/>\nDr B\u00e9atrice Cousin \u2013 beatrice.cousin@inserm.fr &amp; Dr Agn\u00e8s Costes \u2013 agnes.coste@univ-tlse3.fr<\/span><\/p>\n<h2>Identification of targetable molecules causally involved in age-related immune cell defects<\/h2>\n<p><img loading=\"lazy\" decoding=\"async\" class=\" wp-image-1078 alignleft\" src=\"https:\/\/ihuhealthage.fr\/wp-content\/uploads\/2020\/05\/unnamed-2.png\" alt=\"\" width=\"142\" height=\"71\" \/>T cell-mediated immune responses are compromised in aged individuals, leading to increased frequency and severity of infectious diseases and impaired responsiveness to vaccination. The activity of T cells is dependent on the T-cell antigen receptor (TCR), which detects with high sensitivity antigenic peptides associated with molecules of the major histocompatibility complex (MHC) at the surface of antigen presenting cells (APC). In this study, we propose to combine high throughput systemic approaches to systematically investigate the effect of aging on TCR signaling and immunological synapse formation both in human and mouse T cells.<\/p>\n<p>&nbsp;<\/p>\n<h2>Role of age-associated B cells in humoral immunity<\/h2>\n<p><img loading=\"lazy\" decoding=\"async\" class=\" wp-image-1078 alignleft\" src=\"https:\/\/ihuhealthage.fr\/wp-content\/uploads\/2020\/05\/unnamed-2.png\" alt=\"\" width=\"142\" height=\"71\" \/>Our project is to study the role of age -associated B cells in germinal center responses and high-affinity antibody production.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<h2>Functional characterization of dendritic cell functions in the course of aging<\/h2>\n<p><img loading=\"lazy\" decoding=\"async\" class=\" wp-image-1078 alignleft\" src=\"https:\/\/ihuhealthage.fr\/wp-content\/uploads\/2020\/05\/unnamed-2.png\" alt=\"\" width=\"142\" height=\"71\" \/>The development of an immune response is regulated by complex interactions between dendritic cells (DC) and T cells. Distinct subsets of DC are distributed throughout the body and can be distinguished based on phenotypic markers, transcriptional programs, tissue distribution and function. Our hypothesis is that aging may modulate the network of tissue specific factors that instruct DC function during differentiation. Our project aims at characterizing this network to identify new targets to reprogram DC function in elderly.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<h2>Hepatitis E Virus genotype 3 infection in the elderly and immune response<\/h2>\n<p><img loading=\"lazy\" decoding=\"async\" class=\" wp-image-1078 alignleft\" src=\"https:\/\/ihuhealthage.fr\/wp-content\/uploads\/2020\/05\/unnamed-2.png\" alt=\"\" width=\"142\" height=\"71\" \/>Aging is associated with increased susceptibility to infection with various pathogens including Hepatitis E virus genotype 3 (HEV-3). However, the outcome of HEV-3 infection differs among the elderly. To elucidate the mechanism underlying this pathogenesis, we propose to compare key features of peripheral CD8 T cells in infected patients (aged \u226560) with distinct clinical outcomes both at the acute and convalescence period of the infection.<span class=\"Apple-converted-space\">\u00a0<\/span><b><i>\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0<\/i><\/b><\/p>\n<h2>Behavioral assessment of the impact of aging, neurodegeneration and brain infections<\/h2>\n<p><img loading=\"lazy\" decoding=\"async\" class=\" wp-image-1084 alignleft\" src=\"https:\/\/ihuhealthage.fr\/wp-content\/uploads\/2020\/05\/1544537282-406x300.png\" alt=\"\" width=\"89\" height=\"66\" srcset=\"https:\/\/inspire.chu-toulouse.fr\/wp-content\/uploads\/2020\/05\/1544537282-406x300.png 406w, https:\/\/inspire.chu-toulouse.fr\/wp-content\/uploads\/2020\/05\/1544537282-1110x821.png 1110w, https:\/\/inspire.chu-toulouse.fr\/wp-content\/uploads\/2020\/05\/1544537282-768x568.png 768w, https:\/\/inspire.chu-toulouse.fr\/wp-content\/uploads\/2020\/05\/1544537282.png 1461w\" sizes=\"auto, (max-width: 89px) 100vw, 89px\" \/><img loading=\"lazy\" decoding=\"async\" class=\" wp-image-1086 alignleft\" src=\"https:\/\/ihuhealthage.fr\/wp-content\/uploads\/2020\/05\/logo-3.png\" alt=\"\" width=\"68\" height=\"63\" \/>(Supported by the Fondation Recherche M\u00e9dicale\/France Alzheimer). This project will investigate how chronic infections of the central nervous system could contribute to the development and\/or evolution of Alzheimer&rsquo;s disease. We will study in an animal model, how the infestation by a parasite modulates the course of disease, both at the pathological and behavioral levels and we will investigate which immune cell populations may contribute to pathogenesis. These animal studies will be compared to our findings concerning human immune cell populations that we will have identified in the blood of \u00ab\u00a0frail\u00a0\u00bb patients, followed within the \u00ab\u00a0COG-FRAIL\u00a0\u00bb cohort. Our long-term goal will be to identify new predictive biomarkers for the severity and\/or cognitive decline of the patients.<span class=\"Apple-converted-space\">\u00a0<\/span><\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The projects aim to \u00a0better characterize at the cellular and molecular levels the correlates of immune-senescence and inflammaging; \u00a0to pinpoint the pathways associated with specific immune alterations during biological aging. Identification of a specific monocyte signature to predict macrophage pro-inflammatory \/ pro-resolutive status during frailty phenotype Inflammaging corresponds to a gradually augmenting inflammatory state associated [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-618","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Immunity and inflammation - IHU Healthage<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ihuhealthage.fr\/fr\/immunity-and-inflammation\/\" \/>\n<meta property=\"og:locale\" content=\"fr_FR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Immunity and inflammation - IHU Healthage\" \/>\n<meta property=\"og:description\" content=\"The projects aim to \u00a0better characterize at the cellular and molecular levels the correlates of immune-senescence and inflammaging; \u00a0to pinpoint the pathways associated with specific immune alterations during biological aging. 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