{"id":55128,"date":"2026-02-05T09:38:04","date_gmt":"2026-02-05T08:38:04","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/02\/05\/gene-regulatory-programs-of-nk-cells-show-that-ncam1-cd56-and-kirs-are-controlled-by-genetically-polymorphic-distal-regulatory-elements-valuemariam-a-salem-aditi-varkey-matthew-d-es\/"},"modified":"2026-02-05T09:38:04","modified_gmt":"2026-02-05T08:38:04","slug":"gene-regulatory-programs-of-nk-cells-show-that-ncam1-cd56-and-kirs-are-controlled-by-genetically-polymorphic-distal-regulatory-elements-valuemariam-a-salem-aditi-varkey-matthew-d-es","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/02\/05\/gene-regulatory-programs-of-nk-cells-show-that-ncam1-cd56-and-kirs-are-controlled-by-genetically-polymorphic-distal-regulatory-elements-valuemariam-a-salem-aditi-varkey-matthew-d-es\/","title":{"rendered":"Gene Regulatory Programs of NK Cells Show That NCAM1 (CD56) and KIRs Are Controlled by Genetically Polymorphic Distal Regulatory Elements. [[{&#8220;value&#8221;:&#8221;Mariam A. Salem, \nAditi Varkey, \nMatthew D. Estrada, \nKruthika Sharma, \nCaprice D. Eisele, \nNitin Chakravarti, \nDean A. Lee, \nAharon G. Freud, \nBethany L. Mundy\u2010Bosse, \nPatrick L. Collins&#8221;}]]"},"content":{"rendered":"<p><img decoding=\"async\" src=\"https:\/\/onlinelibrary.wiley.com\/cms\/asset\/c5e7c690-741f-4099-99c0-9e85eda94dec\/eji70142-gra-0001-m.png\" alt=\"Gene Regulatory Programs of NK Cells Show That NCAM1 (CD56) and KIRs Are Controlled by Genetically Polymorphic Distal Regulatory Elements\" \/><\/p>\n<p>A deeper understanding of the natural killer cell gene expression regulation driving NK cell maturation and cytotoxicity could provide critical insights into optimizing NK therapies. Our findings reveal novel enhancers governing NK cell genes for NCAM1\/CD56 and cis-regulation for KIR receptors and clarify existing models of NK cell cis-accessibility regulation.<\/p>\n<p><\/p>\n<h2>ABSTRACT<\/h2>\n<p>Owing to their immunoprotective properties, natural killer (NK) cells are critical for the innate immune response to pathogens, as well as a new wave of cancer immunotherapy that harnesses natural cytotoxicity. We sought to study the genetic and epigenetic drivers behind human-specific NK cell receptors, so that we can better understand the underlying cellular function. Here, we present a transcriptomic, proteomic (CITE-seq), and chromatin (single nuclei ATAC-seq) profiling of human peripheral NK cell subsets, which was then compared with genomic databases. Through integrative multi-omics, we demonstrate that CD56<sup>bright<\/sup> versus CD56<sup>dim<\/sup> NK cell subsets have differential distal regulatory element (DRE) landscapes, with fewer accessible DREs in the CD56<sup>dim<\/sup> NK cells. We combine our epigenetic data, deposited Hi-C, and human genetic data to show mechanisms governing the <i>NCAM1<\/i> (encoding CD56) and the killer cell immunoglobulin-like receptors (KIRs) loci. We identify an <i>NCAM1<\/i> DRE that binds STAT3 in most NK cells, while identifying a genetic cohort that has motifs for binding repressive BLIMP1 at the DRE and resulting in less CD56 expression. Together, our findings reveal novel epigenetic and transcriptomic systems for the regulation of NK cell receptors driving NK cell cytotoxicity and diversity.<\/p>","protected":false},"excerpt":{"rendered":"<p>A deeper understanding of the natural killer cell gene expression regulation driving NK cell maturation and cytotoxicity could provide critical insights into optimizing NK therapies. Our findings reveal novel enhancers governing NK cell genes for NCAM1\/CD56 and cis-regulation for KIR receptors and clarify existing models of NK cell cis-accessibility regulation. ABSTRACT Owing to their immunoprotective &#8230; <a title=\"Gene Regulatory Programs of NK Cells Show That NCAM1 (CD56) and KIRs Are Controlled by Genetically Polymorphic Distal Regulatory Elements. [[{&#8220;value&#8221;:&#8221;Mariam A. Salem, \nAditi Varkey, \nMatthew D. Estrada, \nKruthika Sharma, \nCaprice D. Eisele, \nNitin Chakravarti, \nDean A. Lee, \nAharon G. Freud, \nBethany L. Mundy\u2010Bosse, \nPatrick L. Collins&#8221;}]]\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/02\/05\/gene-regulatory-programs-of-nk-cells-show-that-ncam1-cd56-and-kirs-are-controlled-by-genetically-polymorphic-distal-regulatory-elements-valuemariam-a-salem-aditi-varkey-matthew-d-es\/\" aria-label=\"Read more about Gene Regulatory Programs of NK Cells Show That NCAM1 (CD56) and KIRs Are Controlled by Genetically Polymorphic Distal Regulatory Elements. [[{&#8220;value&#8221;:&#8221;Mariam A. Salem, \nAditi Varkey, \nMatthew D. Estrada, \nKruthika Sharma, \nCaprice D. Eisele, \nNitin Chakravarti, \nDean A. Lee, \nAharon G. Freud, \nBethany L. Mundy\u2010Bosse, \nPatrick L. Collins&#8221;}]]\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[112,42],"tags":[],"class_list":["post-55128","post","type-post","status-publish","format-standard","hentry","category-european-journal-of-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/55128","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=55128"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/55128\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=55128"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=55128"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=55128"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}