{"id":109797,"date":"2011-01-07T00:00:00","date_gmt":"2011-01-07T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/polarizacion-th17-en-linfocitos-t-humanos-por-celulas-presentadoras-de-anta%c2%adgeno-profesionales\/"},"modified":"2011-01-07T00:00:00","modified_gmt":"2011-01-07T00:00:00","slug":"polarizacion-th17-en-linfocitos-t-humanos-por-celulas-presentadoras-de-anta%c2%adgeno-profesionales","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/inmunoquimica\/polarizacion-th17-en-linfocitos-t-humanos-por-celulas-presentadoras-de-anta%c2%adgeno-profesionales\/","title":{"rendered":"Polarizaci\u00f3n th17 en linfocitos t humanos por c\u00e9lulas presentadoras de ant\u00edgeno profesionales"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Ismael Ranz Jim\u00e9nez <\/strong><\/h2>\n<p>The characterization of \u00c2\u00bftype 17\u00c2\u00bf human memory helper t-cells (th17) and th1\/17 (ie.: Ifn\u00c2\u00bf e il-17 dual producers) was published during academic year 2007-08 papers just to starting this ph.D. Thesis, which revealed that th17 y th1\/17 frequencies in the circulation were markedly lower than those of th1 or th2 cells. They represented ~10% and ~1% of the th1 blood numbers, respectively. Th1 and th17 instruction was originally attributed to selective \u00c2\u00bfpolarization\u00c2\u00bf mechanisms driven by professional antigen presenting cells (apc), that were opposed and memorized or developmentally fixed for each th-type. Thus, th na\u00ed\u00afve cells were proposed to develop into th17 ccr6+ memory cells in secondary lymphoid organs after instruction by classic monocytes (cmo), which have a selective lymph node migration pattern. A paradox in current th17 activation model is that memory th17 y th1\/17 frequencies do not increase in the blood of patients suffering several autoimmune diseases with markedly increased ccr6+ th1\/17 and th17 cell numbers in their lesions, who further show tissue frequencies similar between th1\/17, th17 and th1 cells despite their differences in the blood pool. Prior work in the mouse model had facilitated the pathway to define cytokine cocktails implicated in \u00c2\u00bfth17 polarization\u00c2\u00bf of  na\u00ed\u00afve t cells in apc-free models, and underlined the relevance of asymmetric cell growth and \u00c2\u00bfplasticity\u00c2\u00bf between th types to account for the balance among th1\/th1\/17\/th17 memory effector cells in lesions.    Herein we examined a novel mechanism to address whether it may explain the counterintuitive high numbers of ccr6+ th1\/17 and th17 effector memory t cells in tissue lesions. The hypothesis was that a non-classic monocyte-dendritic subset (ncmo) termed m-dc8+ after their morphology, that scans inflammed endothelium and migrates to tissue where they encounter th memory cells which infiltrate tissue lesions in a ccr6-driven way, should instruct into proinflammatory th-type responses. Predictions from our hypothesis were an m-c8+ dc-dependent regulation of t-type proliferation favoring asymmetric growth of th1\/17 and th17 cells directly and\/or indirectly through developmental plasticity in th phenotypes following repolarization in a  th1\u00c2\u00bfth1\/17 \u00c2\u00bfth17 precursor-product pathway.     Dc m-dc8+ and th memory cells were purified by automated magnetic cells sorting (automacs\u00c2\u00bf). The frequencies of individual cells producing il17, il-22 and\/or ifn\u00c2\u00bf within their in generations, and their patterns of expression of t-bet and ror\u00c2\u00bft nuclear factors implicated in th1 and th17 commitment was quantitated by th cell staining with cfse cell-division tracker and specific antibodies in immunofluorescence and multiplex flowcytometry assays. Cytokine secretion was assessed by multiplex bead immunoassays.     Our results showed that ccr6+ th1, th17 and th1\/17 memory cells proliferated in a dc m-dc8+-dependent manner, through a mechanism that was accompanied by th1\u00c2\u00bfth1\/17 repolarization driven by augmented ror\u00c2\u00bft transcription factor expression in those cells. All together it accounted for the marked and equilibrated expansion of th1, th17 and th1\/17 effector memory subsets. The il-12\/il-23 balance was key to regulate the above repolarization through t-bet y ror\u00c2\u00bft levels modulation. Our system allowed to investigate the role of cytokines that have been implicated in na\u00ed\u00afve th cell polarization in the above proliferation\/differentiation mechanisms, and more interestingly to show that it is suitable to address the implication of third party cells in th17 regulation, ie.: Nk reduced il-17 production. Ex vivo modelization of dc m-dc8+-driven th memory activation in lesions may contribute to the discovery and assay of novel cellular and molecular targets relevant to control chronic compound proinflammatory th that implicate th1, th17 and th22 cells, which is also needed to improve our rational to use biological response modifier drugs in inflammation infection, transplantation and cancer.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Polarizaci\u00f3n th17 en linfocitos t humanos por c\u00e9lulas presentadoras de ant\u00edgeno profesionales<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Polarizaci\u00f3n th17 en linfocitos t humanos por c\u00e9lulas presentadoras de ant\u00edgeno profesionales <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Ismael Ranz Jim\u00e9nez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Alcal\u00e1<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 01\/07\/2011<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Antonio De La Hera Mart\u00ednez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Carlos Martinez alonso <\/li>\n<li>Jos\u00e9 Alberto Garc\u00eda sanz (vocal)<\/li>\n<li>Juan  Manuel Casas fernandez de tejerina (vocal)<\/li>\n<li>Mar\u00eda  Luisa Gaspar alonso vega (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Ismael Ranz Jim\u00e9nez The characterization of \u00c2\u00bftype 17\u00c2\u00bf human memory helper t-cells (th17) and th1\/17 (ie.: Ifn\u00c2\u00bf [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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