{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T21:37:53Z","timestamp":1783719473923,"version":"3.55.0"},"reference-count":82,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T00:00:00Z","timestamp":1499299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 938"],"award-info":[{"award-number":["SFB 938"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Hyporesponsiveness of human lamina propria immune cells to microbial and nutritional antigens represents one important feature of intestinal homeostasis. It is at least partially mediated by low expression of the innate response receptors CD11b, CD14, CD16 as well as the cystine\u2010glutamate transporter xCT on these cells. Milieu\u2010specific mechanisms leading to the down\u2010regulation of these receptors on circulating monocytes, the precursor cells of resident macrophages, are mostly unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we addressed the question whether the short chain fatty acid n\u2010butyrate, a fermentation product of the mammalian gut microbiota exhibiting histone deacetylase inhibitory activity, is able to modulate expression of these receptors in human circulating monocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exposure to n\u2010butyrate resulted in the downregulation of CD11b, CD14, as well as CD16 surface expression on circulating monocytes. XCT transcript levels in circulating monocytes were also reduced following exposure to n\u2010butyrate. Importantly, treatment resulted in the downregulation of protein and gene expression of the transcription factor PU.1, which was shown to be at least partially required for the expression of CD16 in circulating monocytes. PU.1 expression in resident macrophages in situ was observed to be substantially lower in healthy when compared to inflamed colonic mucosa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In summary, the intestinal microbiota may support symbiosis with the human host organism by n\u2010butyrate mediated downregulation of protein and gene expression of innate response receptors as well as xCT on circulating monocytes following recruitment to the lamina propria. Downregulation of CD16 gene expression may at least partially be caused at the transcriptional level by the n\u2010butyrate mediated decrease in expression of the transcription factor PU.1 in circulating monocytes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.184","type":"journal-article","created":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T07:52:50Z","timestamp":1499327570000},"page":"480-492","source":"Crossref","is-referenced-by-count":21,"title":["Human monocytes downregulate innate response receptors following exposure to the microbial metabolite n\u2010butyrate"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3212-1881","authenticated-orcid":false,"given":"Felix","family":"Lasitschka","sequence":"first","affiliation":[{"name":"Institute of Pathology University Hospital Heidelberg Im Neuenheimer Feld 224 69120 Heidelberg Germany"},{"name":"Institute of Immunology University Hospital Heidelberg Im Neuenheimer Feld 305 69120 Heidelberg 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