{"id":184142,"date":"2024-03-01T21:24:14","date_gmt":"2024-03-02T03:24:14","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2024\/03\/nfil3-contributes-to-cytotoxic-t-lymphocyte-mediated-killing"},"modified":"2024-03-01T21:24:14","modified_gmt":"2024-03-02T03:24:14","slug":"nfil3-contributes-to-cytotoxic-t-lymphocyte-mediated-killing","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2024\/03\/nfil3-contributes-to-cytotoxic-t-lymphocyte-mediated-killing","title":{"rendered":"NFIL3 contributes to cytotoxic T lymphocyte-mediated killing"},"content":{"rendered":"<p style=\"padding-right: 20px\"><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/nfil3-contributes-to-cytotoxic-t-lymphocyte-mediated-killing3.jpg\"><\/a><\/p>\n<p>Cytotoxic T-lymphocytes are important effectors in the clearance of virally infected and cancerous cells, and defects in their function give rise to many pathologies.<\/p>\n<hr>\n<p>Cytotoxic T lymphocytes (CTLs) are key effectors of the adaptive immune system that recognize and eliminate virally infected and cancerous cells. In naive CD8<sup>+<\/sup> T cells, T-cell receptor (TCR) engagement drives a number of transcriptional, translational and proliferation changes over the course of hours and days leading to differentiation into CTLs. To gain a better insight into this mechanism, we compared the transcriptional profiles of naive CD8<sup>+<\/sup> T cells to those of activated CTLs. To find new regulators of CTL function, we performed a selective clustered regularly interspaced short palindromic repeats (CRISPR) screen on upregulated genes and identified nuclear factor IL-3 (NFIL3) as a potential regulator of cytotoxicity. Although NFIL3 has established roles in several immune cells including natural killer, Treg, dendritic and CD4<sup>+<\/sup> T cells, its function in CD8<sup>+<\/sup> CTLs is less well understood. Using CRISPR\/Cas9 editing, we found that removing NFIL3 in CTLs resulted in a marked decrease in cytotoxicity. We found that in CTLs lacking NFIL3 TCR-induced extracellular signal-regulated kinase phosphorylation, immune synapse formation and granule release were all intact while cytotoxicity was functionally impaired <i>in vitro<\/i>. Strikingly, NFIL3 controls the production of cytolytic proteins as well as effector cytokines. Thus, NFIL3 plays a cell intrinsic role in modulating cytolytic mechanisms in CTLs.<\/p>\n<p>CD8<sup>+<\/sup> cytotoxic T lymphocytes (CTLs) are key effectors of the adaptive immune response that precisely recognize and eliminate virally infected and cancerous cells. In naive CD8<sup>+<\/sup> T cells, T-cell receptor (TCR) engagement induces a number of transcriptional, translational and proliferation changes over the course of hours and days leading to differentiation into CTLs [1,2]. TCR ligation of differentiated CTLs drives a rapid response and the formation of a transient area of plasma membrane specialized in signalling and polarized secretion, termed the immune synapse [3]. CTLs undergo rapid rearrangements in microtubule and actin cytoskeletons as the centrosome and microtubule network polarize towards the synapse and cortical actin is transiently depleted [4\u20137].<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Cytotoxic T-lymphocytes are important effectors in the clearance of virally infected and cancerous cells, and defects in their function give rise to many pathologies. Cytotoxic T lymphocytes (CTLs) are key effectors of the adaptive immune system that recognize and eliminate virally infected and cancerous cells. In naive CD8+ T cells, T-cell receptor (TCR) engagement drives [\u2026]<\/p>\n","protected":false},"author":662,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,412],"tags":[],"class_list":["post-184142","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-genetics"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/184142","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/662"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=184142"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/184142\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=184142"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=184142"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=184142"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}