{"id":6465,"date":"2021-11-24T11:32:40","date_gmt":"2021-11-24T11:32:40","guid":{"rendered":"https:\/\/www.adacyte.com\/?post_type=scientific-corner&#038;p=6465"},"modified":"2024-05-02T09:37:43","modified_gmt":"2024-05-02T07:37:43","slug":"circulating-metabolomic-signature-in-generalized-pustular-psoriasis-blunts-monocyte-hyperinflammation-by-triggering-amino-acid-response","status":"publish","type":"scientific-corner","link":"https:\/\/www.adacyte.com\/es\/professional\/scientific-corner\/circulating-metabolomic-signature-in-generalized-pustular-psoriasis-blunts-monocyte-hyperinflammation-by-triggering-amino-acid-response\/","title":{"rendered":"Circulating Metabolomic Signature in Generalized Pustular Psoriasis Blunts Monocyte Hyperinflammation by Triggering Amino Acid Response"},"content":{"rendered":"<div class=\"post-content max-w-987 mx-auto px-20 lg:px-0\">\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Yu+N&amp;cauthor_id=34567002\">Ning Yu<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/#affiliation-1\">1<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Peng+C&amp;cauthor_id=34567002\">Chen Peng<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/#affiliation-1\">1<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Chen+W&amp;cauthor_id=34567002\">Wenjuan Chen<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/#affiliation-1\">1<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Sun+Z&amp;cauthor_id=34567002\">Ziwen Sun<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/#affiliation-1\">1<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Zheng+J&amp;cauthor_id=34567002\">Jianfeng Zheng<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/#affiliation-1\">1<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Zhang+S&amp;cauthor_id=34567002\">Shujie Zhang<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/#affiliation-2\">2<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Ding+Y&amp;cauthor_id=34567002\">Yangfeng Ding<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/#affiliation-1\">1<\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Shi+Y&amp;cauthor_id=34567002\">Yuling Shi<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/#affiliation-1\">1<\/a><\/sup> , <\/p>\n<\/div>\n\n<div class=\"post-content max-w-987 mx-auto px-20 lg:px-0\">\n<p>Front Immunol<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/nlmcatalog?term=%22Front+Immunol%22%5BTitle+Abbreviation%5D\"><\/a><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/#\"><\/a>.\u00a02021 Sep 8;12:739514.\u00a0doi: 10.3389<\/p>\n<\/div>\n\n<div class=\"post-content max-w-987 mx-auto px-20 lg:px-0\">\n<p>Generalized pustular psoriasis (GPP), the most grievous variant of psoriasis, is featured by dysregulated systemic inflammatory response. The cellular and molecular basis of GPP is poorly understood. Blood monocytes are key players of host defense and producers of inflammatory cytokines including IL-1\u03b2. How the immune response of monocytes is affected by metabolic internal environment in GPP remains unclear. Here, we performed a metabolomic and functional investigation of GPP serum and monocytes. We demonstrated a significant increase in IL-1\u03b2 production from GPP monocytes. In GPP circulation, serum amyloid A (SAA), an acute-phase reactant, was dramatically increased, which induced the release of IL-1\u03b2 from monocytes in a NLRP3-dependent manner. Using metabolomic analysis, we showed that GPP serum exhibited an amino acid starvation signature, with glycine, histidine, asparagine, methionine, threonine, lysine, valine, isoleucine, tryptophan, tyrosine, alanine, proline, taurine and cystathionine being markedly downregulated. In functional assay, under amino acid starvation condition, SAA-stimulated mature IL-1\u03b2 secretion was suppressed. Mechanistically, at post-transcriptional level, amino acid starvation inhibited the SAA-mediated reactive oxygen species (ROS) formation and NLRP3 inflammasome activation. Moreover, the immune-modulatory effect of amino acid starvation was blocked by silencing general control nonderepressible 2 kinase (GCN2), suggesting the involvement of amino acid response (AAR) pathway. Collectively, our results suggested that decreased serum amino acids in GPP blunted the innate immune response in blood monocytes through AAR pathway, serving as a feedback mechanism preventing excessive inflammation in GPP.<\/p>\n<\/div>\n\n<div class=\"post-content max-w-987 mx-auto px-20 lg:px-0\">\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/\">https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/<\/a><\/p>\n<\/div>\n\n<div class=\"post-content max-w-987 mx-auto px-20 lg:px-0\">\n<p><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Ning Yu\u00a01,\u00a0Chen Peng\u00a01,\u00a0Wenjuan Chen\u00a01,\u00a0Ziwen Sun\u00a01,\u00a0Jianfeng Zheng\u00a01,\u00a0Shujie Zhang\u00a02,\u00a0Yangfeng Ding\u00a01,\u00a0Yuling Shi\u00a01 , Front Immunol.\u00a02021 Sep 8;12:739514.\u00a0doi: 10.3389 Generalized pustular psoriasis (GPP), the most grievous variant of psoriasis, is featured by dysregulated systemic inflammatory response. The cellular and molecular basis of GPP is poorly understood. Blood monocytes are key players of host defense and producers of inflammatory cytokines [&hellip;]<\/p>\n","protected":false},"template":"","scientific_tags":[455,454,107,67],"class_list":["post-6465","scientific-corner","type-scientific-corner","status-publish","hentry","scientific_tags-amino-acid","scientific_tags-metabolomics","scientific_tags-monocyte","scientific_tags-pustular-psoriasis"],"acf":{"sc_authors":"<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/\">https:\/\/pubmed.ncbi.nlm.nih.gov\/34567002\/<\/a>"},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v22.9 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Circulating Metabolomic Signature in Generalized Pustular Psoriasis Blunts Monocyte Hyperinflammation by Triggering Amino Acid Response - Adacyte<\/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:\/\/www.adacyte.com\/professional\/scientific-corner\/circulating-metabolomic-signature-in-generalized-pustular-psoriasis-blunts-monocyte-hyperinflammation-by-triggering-amino-acid-response\/\" \/>\n<meta property=\"og:locale\" content=\"es_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Circulating Metabolomic Signature in Generalized Pustular Psoriasis Blunts Monocyte Hyperinflammation by Triggering Amino Acid Response - Adacyte\" \/>\n<meta property=\"og:description\" content=\"Ning Yu\u00a01,\u00a0Chen Peng\u00a01,\u00a0Wenjuan Chen\u00a01,\u00a0Ziwen Sun\u00a01,\u00a0Jianfeng Zheng\u00a01,\u00a0Shujie Zhang\u00a02,\u00a0Yangfeng Ding\u00a01,\u00a0Yuling Shi\u00a01 , Front Immunol.\u00a02021 Sep 8;12:739514.\u00a0doi: 10.3389 Generalized pustular psoriasis (GPP), the most grievous variant of psoriasis, is featured by dysregulated systemic inflammatory response. The cellular and molecular basis of GPP is poorly understood. Blood monocytes are key players of host defense and producers of inflammatory cytokines [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.adacyte.com\/professional\/scientific-corner\/circulating-metabolomic-signature-in-generalized-pustular-psoriasis-blunts-monocyte-hyperinflammation-by-triggering-amino-acid-response\/\" \/>\n<meta property=\"og:site_name\" content=\"Adacyte\" \/>\n<meta property=\"article:modified_time\" content=\"2024-05-02T07:37:43+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Tiempo de lectura\" \/>\n\t<meta name=\"twitter:data1\" content=\"2 minutos\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/www.adacyte.com\/professional\/scientific-corner\/circulating-metabolomic-signature-in-generalized-pustular-psoriasis-blunts-monocyte-hyperinflammation-by-triggering-amino-acid-response\/\",\"url\":\"https:\/\/www.adacyte.com\/professional\/scientific-corner\/circulating-metabolomic-signature-in-generalized-pustular-psoriasis-blunts-monocyte-hyperinflammation-by-triggering-amino-acid-response\/\",\"name\":\"Circulating Metabolomic Signature in Generalized Pustular Psoriasis Blunts Monocyte Hyperinflammation by Triggering Amino Acid Response - Adacyte\",\"isPartOf\":{\"@id\":\"https:\/\/www.adacyte.com\/#website\"},\"datePublished\":\"2021-11-24T11:32:40+00:00\",\"dateModified\":\"2024-05-02T07:37:43+00:00\",\"inLanguage\":\"es\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/www.adacyte.com\/professional\/scientific-corner\/circulating-metabolomic-signature-in-generalized-pustular-psoriasis-blunts-monocyte-hyperinflammation-by-triggering-amino-acid-response\/\"]}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/www.adacyte.com\/#website\",\"url\":\"https:\/\/www.adacyte.com\/\",\"name\":\"Adacyte\",\"description\":\"Adacyte Therapeutics\",\"publisher\":{\"@id\":\"https:\/\/www.adacyte.com\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/www.adacyte.com\/?s={search_term_string}\"},\"query-input\":\"required name=search_term_string\"}],\"inLanguage\":\"es\"},{\"@type\":\"Organization\",\"@id\":\"https:\/\/www.adacyte.com\/#organization\",\"name\":\"Adacyte\",\"url\":\"https:\/\/www.adacyte.com\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"es\",\"@id\":\"https:\/\/www.adacyte.com\/#\/schema\/logo\/image\/\",\"url\":\"https:\/\/www.adacyte.com\/wp-content\/uploads\/2021\/01\/logo-adacyte.svg\",\"contentUrl\":\"https:\/\/www.adacyte.com\/wp-content\/uploads\/2021\/01\/logo-adacyte.svg\",\"width\":165,\"height\":46,\"caption\":\"Adacyte\"},\"image\":{\"@id\":\"https:\/\/www.adacyte.com\/#\/schema\/logo\/image\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Circulating Metabolomic Signature in Generalized Pustular Psoriasis Blunts Monocyte Hyperinflammation by Triggering Amino Acid Response - Adacyte","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.adacyte.com\/professional\/scientific-corner\/circulating-metabolomic-signature-in-generalized-pustular-psoriasis-blunts-monocyte-hyperinflammation-by-triggering-amino-acid-response\/","og_locale":"es_ES","og_type":"article","og_title":"Circulating Metabolomic Signature in Generalized Pustular Psoriasis Blunts Monocyte Hyperinflammation by Triggering Amino Acid Response - Adacyte","og_description":"Ning Yu\u00a01,\u00a0Chen Peng\u00a01,\u00a0Wenjuan Chen\u00a01,\u00a0Ziwen Sun\u00a01,\u00a0Jianfeng Zheng\u00a01,\u00a0Shujie Zhang\u00a02,\u00a0Yangfeng Ding\u00a01,\u00a0Yuling Shi\u00a01 , Front Immunol.\u00a02021 Sep 8;12:739514.\u00a0doi: 10.3389 Generalized pustular psoriasis (GPP), the most grievous variant of psoriasis, is featured by dysregulated systemic inflammatory response. The cellular and molecular basis of GPP is poorly understood. 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